Faculty Profiles - TAMURA Takashi

The Significance of Comprehensive Metabolic Phenotypes in Cancer Risk: A Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. Reviewed International journal Open Access

Takeshi Watanabe, Tien Van Nguyen, Sakurako Katsuura-Kamano, Kokichi Arisawa, Masashi Ishizu, Taichi Unohara, Keitaro Tanaka, Chisato Shimanoe, Mako Nagayoshi, Takashi Tamura, Yoko Kubo, Yasufumi Kato, Isao Oze, Hidemi Ito, Nobuaki Michihata, Yohko Nakamura, Shiroh Tanoue, Chihaya Koriyama, Sadao Suzuki, Hiroko Nakagawa-Senda, Teruhide Koyama, Satomi Tomida, Kiyonori Kuriki, Naoyuki Takashima, Akiko Harada, Kenji Wakai, Keitaro Matsuo

Cancer research communications Vol. 4 ( 11 ) page： 2986 - 2997 2024.11

Language：English Publishing type：Research paper (scientific journal)

The present study investigated the relationship between metabolic phenotypes and the risk of cancer in a Japanese population using the criteria of metabolic phenotypes based on an examination and those based on questionnaires. We used data from 25,357 subjects for examination-based analyses and those from 53,042 subjects for questionnaire-based analyses in the Japan Multi-Institutional Collaborative Cohort Study. Metabolic phenotypes were defined by classifying subjects according to their BMI (obesity: BMI ≥25 kg/m2; normal weight: BMI <25 kg/m2) and the number of metabolic abnormalities. Metabolic abnormalities were defined according to metabolic syndrome components of the Joint Interim Statement Criteria for examination-based analyses and self-reported histories of diabetes, dyslipidemia, and hypertension for questionnaire-based analyses. Cox proportional hazards regression analyses adjusted for potential confounders were performed for total and site-specific cancer incidence according to metabolic phenotypes. Metabolically unhealthy obesity (MUHO) was significantly associated with cancer incidence in both examination-based [HR (95% CI): 1.17 (1.01-1.36)] and questionnaire-based analyses [HR (95% CI): 1.15 (1.04-1.26)]. Regarding site-specific cancer in questionnaire-based analyses, metabolically healthy obesity and MUHO were associated with colorectum and liver cancers in all subjects and with breast cancer in female subjects. Subjects with a metabolically unhealthy normal weight had a higher risk of pancreatic cancer. Moreover, MUHO was associated with corpus uteri cancer in female subjects. This prospective cohort study suggests that metabolic phenotypes are important risk factors for total and some site-specific cancers in Japanese adults.

DOI： 10.1158/2767-9764.CRC-24-0249

Food group intakes and high-sensitivity C-reactive protein among community-dwelling Japanese adults: a cross-sectional study. Reviewed International journal Open Access

Takashi Matsunaga, Kenji Wakai, Nahomi Imaeda, Chiho Goto, Yudai Tamada, Yasufumi Kato, Yoko Kubo, Rieko Okada, Mako Nagayoshi, Takashi Tamura, Asahi Hishida, Hiroaki Ikezaki, Jun Otonari, Naoyuki Takashima, Naoko Miyagawa, Keitaro Matsuo

Public health nutrition Vol. 27 ( 1 ) page： e212 2024.10

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Healthy dietary patterns have been linked to lower levels of chronic inflammation. The present study aimed to investigate the associations between food group intakes and high-sensitivity C-reactive protein (hsCRP) among community-dwelling adults. DESIGN: Cross-sectional. SETTING: Three areas in Japan (Shiga, Fukuoka, or Kyushu and Okinawa). PARTICIPANTS: The present analysis included 13 648 participants (5126 males and 8522 females; age range, 35-69 years) who had been enrolled in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. Food group intakes were estimated using a FFQ. Multiple linear regression was used to examine associations between the quartiles of each energy-adjusted food group intake and log-transformed hsCRP. RESULTS: The following concentration ratios of hsCRP after comparing the highest and lowest quartiles of food group intake were significant: in males, 1·12 (95 % CI 1·02, 1·22) for processed meat, 1·13 (95 % CI 1·03, 1·24) for fish and 0·83 (95 % CI 0·76, 0·90) for nuts; in females, 0·89 (95 % CI 0·81, 0·97) for bread, 1·11 (95 % CI 1·03, 1·19) for processed meat, 0·86 (95 % CI 0·80, 0·92) for vegetables, 1·19 (95 % CI 1·11, 1·29) for fruit, 0·90 (95 % CI 0·84, 0·97) for nuts and 0·88 (95 % CI 0·82, 0·95) for green tea. CONCLUSIONS: Processed meat and nut intakes were associated with higher and lower hsCRP levels, respectively, in both sexes. However, for several food groups, including fish and fruit, previous findings from dietary pattern analyses were not supported by the present analyses at the food group level.

DOI： 10.1017/S1368980024001599

Polygenic risk score for blood pressure and lifestyle factors with overall and CVD mortality: a prospective cohort study in a Japanese population. Reviewed International journal

Ryosuke Fujii, Asahi Hishida, Masahiro Nakatochi, Hiroshi Okumiyama, Naoyuki Takashima, Yoshiki Tsuboi, Koji Suzuki, Hiroaki Ikezaki, Chisato Shimanoe, Yasufumi Kato, Takashi Tamura, Hidemi Ito, Nobuaki Michihata, Shiroh Tanoue, Sadao Suzuki, Kiyonori Kuriki, Aya Kadota, Takeshi Watanabe, Yukihide Momozawa, Kenji Wakai, Keitaro Matsuo

Hypertension research : official journal of the Japanese Society of Hypertension Vol. 47 ( 9 ) page： 2284 - 2294 2024.7

Language：English Publishing type：Research paper (scientific journal)

Although previous polygenic risk score (PRS) studies for cardiovascular disease (CVD) focused on incidence, few studies addressed CVD mortality and quantified risks by environmental exposures in different genetic liability groups. This prospective study aimed to examine the associations of blood pressure PRS with all-cause and CVD mortality and to quantify the attributable risk by modifiable lifestyles across different PRS strata. 9,296 participants in the Japan Multi-Institutional Collaborative Cohort Study without hypertension at baseline were analyzed in this analysis. PRS for systolic blood pressure and diastolic blood pressure (PRSSBP and PRSDBP) were developed using publicly available Biobank Japan GWAS summary statistics. CVD-related mortality was defined by the International Classification of Diseases 10th version (I00-I99). Cox-proportional hazard model was used to examine associations of PRSs and lifestyle variables (smoking, drinking, and dietary sodium intake) with mortality. During a median 12.6-year follow-up period, we observed 273 all-cause and 41 CVD mortality cases. Compared to the middle PRS group (20-80th percentile), adjusted hazard ratios for CVD mortality at the top PRS group ( > 90th percentile) were 3.67 for PRSSBP and 2.92 for PRSDBP. Attributable risks of CVD mortality by modifiable lifestyles were higher in the high PRS group ( > 80th percentile) compared with the low PRS group (0-80th percentile). In summary, blood pressure PRS is associated with CVD mortality in the general Japanese population. Our study implies that integrating PRS with lifestyle could contribute to identify target populations for lifestyle intervention even though improvement of discriminatory ability by PRS alone is limited.

DOI： 10.1038/s41440-024-01766-9

Association between awareness of limiting food intake and all-cause mortality: A cohort study in Japan. Reviewed

Association between dysphagia risk and sleep quality in community-dwelling older adults: A cross-sectional study. Reviewed International journal Open Access

Yohko Hama, Sachiko Yamada, Rumi Nishimura, Mitsuyoshi Yoshida, Kazuhiro Tsuga, Emi Morita, Yudai Tamada, Yasufumi Kato, Yoko Kubo, Rieko Okada, Mako Nagayoshi, Takashi Tamura, Asahi Hishida, Kenji Wakai, Mariko Naito

Heliyon Vol. 10 ( 11 ) page： e32028 2024.6

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: Exploring the effects of swallowing function on sleep quality could provide valuable insights into the potential impact of reduced swallowing function on sleep. However, pertinent studies are limited. Therefore, this study aimed to investigate the relationship between dysphagia risk and sleep health in community-dwelling older adults. METHODS: Data for this cross-sectional study were obtained from the Shizuoka and Daiko studies conducted as part of the Japan Multi-Institutional Collaborative Cohort Study. Information on demographics, overall lifestyle, dysphagia risk, as well as sleep quality, duration, satisfaction, and regularity, was obtained using a self-administered questionnaire. Dysphagia risk and sleep quality were assessed using the Dysphagia Risk Assessment Questionnaire for the Community-dwelling Elderly and the Japanese version of the Pittsburgh Sleep Questionnaire Index, respectively. Multivariate logistic regression, adjusted for covariates, was employed to assess the association between dysphagia risk and sleep health. RESULTS: Among the 3058 participants (1633 males, 1425 females) aged ≥60 years, 28.0 % exhibited dysphagia risk, and 19.1 % reported poor sleep quality. Those with dysphagia risk were more likely to experience poor sleep quality than those without dysphagia risk. In male participants, dysphagia was significantly associated with poor sleep quality, unsatisfactory sleep, and sleep irregularity, but was not significantly associated with unsatisfactory or irregular sleep in female participants. The Japanese version of the Pittsburgh Sleep Questionnaire Index components-subjective sleep quality, sleep latency, sleep disturbances, and daytime dysfunction-were associated with dysphagia risk in both sexes. CONCLUSIONS: Dysphagia risk is associated with sleep quality in older individuals in Japan. Thus, preserving swallowing function may contribute to enhancing sleep quality.

DOI： 10.1016/j.heliyon.2024.e32028

Daisaku Nishimoto, Rie Ibusuki, Ippei Shimoshikiryo, Kenichi Shibuya, Shiroh Tanoue, Chihaya Koriyama, Toshiro Takezaki, Isao Oze, Hidemi Ito, Asahi Hishida, Takashi Tamura, Yasufumi Kato, Yudai Tamada, Yuichiro Nishida, Chisato Shimanoe, Sadao Suzuki, Takeshi Nishiyama, Etsuko Ozaki, Satomi Tomida, Kiyonori Kuriki, Naoko Miyagawa, Keiko Kondo, Kokichi Arisawa, Takeshi Watanabe, Hiroaki Ikezaki, Jun Otonari, Kenji Wakai, Keitaro Matsuo

Journal of epidemiology Vol. 34 ( 0 ) page： 286 - 294 2024.6

Language：English Publishing type：Research paper (scientific journal) Publisher：Japan Epidemiological Association

BACKGROUND: Improving diets requires an awareness of the need to limit foods for which excessive consumption is a health problem. Since there are limited reports on the link between this awareness and mortality risk, we examined the association between awareness of limiting food intake (energy, fat, and sweets) and all-cause mortality in a Japanese cohort study. METHODS: Participants comprised 58,772 residents (27,294 men; 31,478 women) aged 35-69 years who completed baseline surveys of the Japan Multi-Institutional Collaborative Cohort Study from 2004 to 2014. Hazard ratios (HRs) for all-cause mortality and 95% confidence intervals (CIs) were estimated by sex using a Cox proportional hazard model, with adjustment for related factors. Mediation analysis with fat intake as a mediator was also conducted. RESULTS: The mean follow-up period was 11 years and 2,516 people died. Estimated energy and fat intakes according to the Food Frequency Questionnaire were lower in those with awareness of limiting food intake than in those without this awareness. Women with awareness of limiting fat intake showed a significant decrease in mortality risk (HR=0.73; 95% CI, 0.55 to 0.94). Mediation analysis revealed that this association was due to the direct effect of the awareness of limiting fat intake and that the total effect was not mediated by actual fat intake. Awareness of limiting energy or sweets intake was not related to mortality risk reduction. CONCLUSION: Awareness of limiting food intake had a limited effect on reducing all-cause mortality risk.

DOI： 10.2188/jea.JE20220354

GWAS of folate metabolism with gene-environment interaction analysis revealed the possible role of lifestyles in the control of blood folate metabolites in Japanese - the J-MICC Study. Reviewed

Elevated level of urinary tellurium is a potential risk for increase of blood pressure in humans and mice. Reviewed International journal Open Access

Tomoko Misawa, Takumi Kagawa, Nobutaka Ohgami, Akira Tazaki, Shoko Ohnuma, Hisao Naito, Dijie Chen, Yishuo Gu, Takashi Tamura, Kenji Wakai, Kimitoshi Nishiwaki, Masashi Kato

Environment international Vol. 188 page： 108735 - 108735 2024.6

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: People worldwide are routinely exposed to tellurium mainly via dietary ingestion. There has been no study to clarify the contribution of tellurium to blood pressure in humans or animals. METHODS: In this cross-sectional study conducted in a general population of 2592 residents in Japan, the associations of urinary tellurium levels with blood pressure and prevalence of hypertension were investigated. The potential sources of tellurium were also investigated. An interventional study in mice confirmed the effect of tellurium exposure on blood pressure. RESULTS: Linear and logistic regression analyses with consideration of confounders including urinary sodium-potassium ratio showed significant positive associations of urinary tellurium level with prevalence of hypertension and blood pressure. Cereals/beans and vegetables/fruits were determined to be potential dietary sources of tellurium exposure. Intermediary analysis suggested that increased intake of cereals/beans, but not that of vegetables/fruits, is positively associated with the tellurium-mediated risk of hypertension. Correspondingly, the mouse study showed that exposure to a putative human-equivalent dose of tellurium via drinking water increased blood pressure with an elevated level of urinary tellurium. The temporally increased blood pressure was decreased to the normal level by a break of tellurium exposure with a reduced level of urinary tellurium. CONCLUSIONS: The interdisciplinary approach provided the first evidence that tellurium exposure is a potential risk for increase of blood pressure. Since the human urinary tellurium level in this study is comparable with the levels in general populations in other Asian and European countries in previous studies, exposure to tellurium may be a latent universal risk for hypertension.

DOI： 10.1016/j.envint.2024.108735

Mineko Tsukamoto, Asahi Hishida, Takashi Tamura, Mako Nagayoshi, Rieko Okada, Yoko Kubo, Yasufumi Kato, Nobuyuki Hamajima, Yuichiro Nishida, Chisato Shimanoe, Rie Ibusuki, Kenichi Shibuya, Naoyuki Takashima, Yasuyuki Nakamura, Miho Kusakabe, Yohko Nakamura, Yuriko N Koyanagi, Isao Oze, Takeshi Nishiyama, Sadao Suzuki, Isao Watanabe, Daisuke Matsui, Jun Otonari, Hiroaki Ikezaki, Sakurako Katsuura-Kamano, Kokichi Arisawa, Kiyonori Kuriki, Masahiro Nakatochi, Yukihide Momozawa, Kenji Takeuchi, Kenji Wakai, Keitaro Matsuo

Journal of epidemiology Vol. 34 page： 228 - 237 2024.5

Language：English Publishing type：Research paper (scientific journal) Publisher：Japan Epidemiological Association

BACKGROUND: The present genome-wide association study (GWAS) aimed to reveal the genetic loci associated with folate metabolites as well as to detect related gene-environment interactions in Japanese. METHODS: We conducted the GWAS of plasma homocysteine (Hcy), folic acid (FA), and vitamin B12 (VB12) levels in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study participants who joined from 2005 to 2012, and also estimated gene-environment interactions. In the replication phase, we used data from the Yakumo Study conducted in 2009. In the discovery phase, data of 2,263 participants from four independent study sites of the J-MICC Study were analyzed. In the replication phase, data of 573 participants from the Yakumo Study were analyzed. RESULTS: For Hcy, MTHFR locus on chr 1, NOX4 on chr 11, CHMP1A on chr 16, and DPEP1 on chr 16 reached genome-wide significance (P < 5×10-8). MTHFR also associated with FA, and FUT2 on chr 19 associated with VB12. We investigated gene-environment interactions in both studies and found significant interactions between MTHFR C677T and ever drinking, current drinking, and physical activity > 33% on Hcy (β = 0.039, 0.038 and -0.054, P = 0.018, 0.021 and < 0.001, respectively) and the interaction of MTHFR C677T with ever drinking on FA (β = 0.033, P = 0.048). CONCLUSIONS: The present GWAS revealed the folate metabolism-associated genetic loci and gene-environment interactions with drinking and physical activity in Japanese, suggesting the possibility of future personalized CVD prevention.

DOI： 10.2188/jea.JE20220341

The Inverse Association between the Frequency of Forest Walking (Shinrin-yoku) and the Prevalence of Insomnia Symptoms in the General Japanese Population: A Japan Multi-Institutional Collaborative Cohort Daiko Study.

Association between consumption of small fish and all-cause mortality among Japanese: the Japan Multi-Institutional Collaborative Cohort Study. Reviewed International journal Open Access

Chinatsu Kasahara, Takashi Tamura, Kenji Wakai, Yudai Tamada, Yasufumi Kato, Yoko Kubo, Rieko Okada, Mako Nagayoshi, Asahi Hishida, Nahomi Imaeda, Chiho Goto, Jun Otonari, Hiroaki Ikezaki, Yuichiro Nishida, Chisato Shimanoe, Isao Oze, Yuriko N Koyanagi, Yohko Nakamura, Miho Kusakabe, Daisaku Nishimoto, Ippei Shimoshikiryo, Sadao Suzuki, Miki Watanabe, Etsuko Ozaki, Chie Omichi, Kiyonori Kuriki, Naoyuki Takashima, Naoko Miyagawa, Kokichi Arisawa, Sakurako Katsuura-Kamano, Kenji Takeuchi, Keitaro Matsuo

Public health nutrition Vol. 27 ( 1 ) page： e135 - 40 2024.5

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Although small fish are an important source of micronutrients, the relationship between their intake and mortality remains unclear. This study aimed to clarify the association between intake of small fish and all-cause and cause-specific mortality. DESIGN: We used the data from a cohort study in Japan. The frequency of the intake of small fish was assessed using a validated food frequency questionnaire. The hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality according to the frequency of the intake of small fish by sex were estimated using a Cox proportional hazard model with adjustments for covariates. SETTING: The Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. PARTICIPANTS: A total of 80,802 participants (34,555 males and 46,247 females), aged 35-69 years. RESULTS: During a mean follow-up of 9.0 years, we identified 2,482 deaths including 1,495 cancer-related deaths. The intake of small fish was statistically significantly and inversely associated with the risk of all-cause and cancer mortality in females. The multivariable-adjusted HRs (95% CIs) in females for all-cause mortality according to the intake were 0.68 (0.55-0.85) for intakes 1-3 times/month, 0.72 (0.57-0.90) for 1-2 times/week, and 0.69 (0.54-0.88) for ≥3 times/week, compared with the rare intake. The corresponding HRs (95% CIs) in females for cancer mortality were 0.72 (0.54-0.96), 0.71 (0.53-0.96), and 0.64 (0.46-0.89), respectively. No statistically significant association was observed in males. CONCLUSIONS: Intake of small fish may reduce the risk of all-cause and cancer mortality in Japanese females.

DOI： 10.1017/S1368980024000831

Morita E, Kadotani H, Yamada N, Sasakabe T, Kawai S, Naito M, Tamura T, Wakai K

International journal of environmental research and public health Vol. 21 ( 3 ) 2024.3

Language：English Publisher：International Journal of Environmental Research and Public Health

Since a single forest walk (Shinrin-yoku or forest bathing) session is reported to improve sleep temporarily, occasional forest walks may have a positive effect on daily sleep. Therefore, this study aimed to examine whether more frequent forest walking is associated with better daily sleep conditions. Data from the second survey of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Daiko Study conducted among residents of Nagoya City, Japan, were used. The study design was a cross-sectional study. In total, 2044 participants (529 men and 1515 women; age, mean ± standard deviation: 58.8 ± 9.9 years) were included in the analysis. Frequent forest walks were associated with a low percentage of insomnia symptoms (Insomnia Severity Index ≥10) in women, but not in men. The adjusted odds ratio for the group that rarely took forest walks with reference to the group that engaged in the activity once a month or more often was 2.04 (95% confidence interval: 1.29–3.23) in women. Forest walk frequency was not significantly associated with sleep duration or sleep efficiency as measured by actigraphy in either men or women. In conclusion, the results suggested that increasing the frequency of forest walks or Shinrin-yoku may be effective in preventing insomnia in women.

DOI： 10.3390/ijerph21030350

BMI and cardiometabolic traits in Japanese: a Mendelian randomization study. Reviewed

Mako Nagayoshi, Asahi Hishida, Tomonori Shimizu, Yasufumi Kato, Yoko Kubo, Rieko Okada, Takashi Tamura, Jun Otonari, Hiroaki Ikezaki, Megumi Hara, Yuichiro Nishida, Isao Oze, Yuriko N Koyanagi, Yohko Nakamura, Miho Kusakabe, Rie Ibusuki, Keiichi Shibuya, Sadao Suzuki, Takeshi Nishiyama, Teruhide Koyama, Etsuko Ozaki, Kiyonori Kuriki, Naoyuki Takashima, Yasuyuki Nakamura, Sakurako Katsuura-Kamano, Kokichi Arisawa, Masahiro Nakatochi, Yukihide Momozawa, Kenji Takeuchi, Kenji Wakai

Journal of epidemiology Vol. 34 page： 51 - 62 2024.2

Language：English Publishing type：Research paper (scientific journal) Publisher：Japan Epidemiological Association

BACKGROUND: Although many observational studies have demonstrated significant relationships between obesity and cardiometabolic traits, the causality of these relationships in East Asians remains to be elucidated. METHODS: We conducted individual-level Mendelian randomization (MR) analyses targeting 14,083 participants in the Japan Multi-Institutional Collaborative Cohort Study, and two-sample MR analyses using summary statistics based on genome-wide association study data from 173,430 Japanese. Using 83 body mass index-related loci, genetic risk scores (GRS) for BMI were calculated, and the effects of BMI on cardiometabolic traits were examined for individual-level MR analyses by the two-stage least squares estimator method. The β-coefficients and standard errors for the per-allele association of each single-nucleotide polymorphism as well as all outcomes, or odds ratios with 95% confidence intervals were calculated in the two-sample MR analyses. RESULTS: In individual-level MR analyses, the GRS of BMI was not significantly associated with any cardiometabolic traits. In two-sample MR analyses, higher BMI was associated with higher risks of higher blood pressure, triglycerides, uric acid, lower high-density-lipoprotein cholesterol and eGFR. The associations of BMI with type 2 diabetes in two-sample MR analyses were inconsistent by different methods, including the directions. CONCLUSIONS: The results of this study suggest that, even among the Japanese, an East Asian population with low levels of obesity, higher BMI could be causally associated with the development of a variety of cardiometabolic traits. Causality in those associations should be clarified in future studies with larger populations, especially those of BMI with type 2 diabetes.

DOI： 10.2188/jea.JE20220154

Seven‐plus hours of daily sedentary time and the subsequent risk of breast cancer: Japan Multi‐Institutional Collaborative Cohort Study Reviewed

Satomi Tomida, Teruhide Koyama, Etsuko Ozaki, Naoyuki Takashima, Midori Morita, Koichi Sakaguchi, Yasuto Naoi, Yuichiro Nishida, Megumi Hara, Asahi Hishida, Takashi Tamura, Rieko Okada, Yoko Kubo, Jun Otonari, Hiroaki Ikezaki, Yohko Nakamura, Miho Kusakabe, Shiroh Tanoue, Chihaya Koriyama, Yuriko N. Koyanagi, Hidemi Ito, Sadao Suzuki, Takahiro Otani, Naoko Miyagawa, Yukiko Okami, Kokichi Arisawa, Takeshi Watanabe, Kiyonori Kuriki, Kenji Wakai, Keitaro Matsuo

Cancer Science Vol. 115 page： 611 - 622 2024.2

Language：English Publishing type：Research paper (scientific journal) Publisher：Wiley

Abstract

This study aimed to investigate the association between daily sedentary time and the risk of breast cancer (BC) in a large Japanese population. The participants were 36,023 women aged 35–69 years from the Japan Multi‐Institutional Collaborative Cohort Study. Cox proportional hazards analysis was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for BC incidence in relation to time spent sedentarily (categorical variables: <7 and ≥7 hours/day [h/d]). Additionally, the associations of BC incidence to the joint effect of sedentary time with each component of physical activity, such as leisure‐time metabolic equivalents (METs), frequency of leisure‐time physical activity, and daily walking time, were examined. During 315,189 person‐years of follow‐up, 554 incident cases of BC were identified. When compared to participants who spent <7 h/d sedentary, those who spent ≥7 h/d sedentary have a significantly higher risk of BC (HR, 1.36; 95% CI, 1.07–1.71). The corresponding HRs among participants who spent ≥7 h/d sedentary with more physical activity, such as ≥1 h/d for leisure‐time METs, ≥3 days/week of leisure‐time physical activity, and ≥1 h/d of daily walking were 1.58 (95% CI, 1.11–2.25), 1.77 (95% CI, 1.20–2.61), and 1.42 (95% CI, 1.10–1.83), respectively, compared with those who spent <7 h/d sedentary. This study found that spending ≥7 h/d of sedentary time is associated with the risk of BC. Neither leisure‐time physical activity nor walking had a BC‐preventive effect in those with ≥7 h/d of sedentary time.

DOI： 10.1111/cas.16020

Elevated arsenic level in fasting serum via ingestion of fish meat increased the risk of hypertension in humans and mice. Reviewed International journal Open Access

Takumi Kagawa, Nobutaka Ohgami, Tingchao He, Akira Tazaki, Shoko Ohnuma, Hisao Naito, Ichiro Yajima, Dijie Chen, Yuqi Deng, Takashi Tamura, Takaaki Kondo, Kenji Wakai, Masashi Kato

European heart journal open Vol. 3 ( 5 ) page： oead074 2023.9

Language：English Publishing type：Research paper (scientific journal)

AIMS: There has been a shortage of human studies to elucidate the association between serum arsenic levels and the prevalence of hypertension. This study multidirectionally investigated associations among arsenic exposure, dietary ingestion, and the risk of hypertension by combined human epidemiological and mouse experimental studies. METHODS AND RESULTS: This study focused on the total arsenic level in fasting serum, a biomarker of arsenic exposure. Associations among ingestion frequencies of 54 diet items of Japanese food separated into six categories, total arsenic level in fasting serum, and the prevalence of hypertension were investigated in 2709 general people in Japan. Logistic regression analysis demonstrated a dose-dependent association between serum arsenic level and hypertension and a positive association between the ingestion of fish meat and hypertension. Further analysis showed that the latter association was fully mediated by increased fasting serum arsenic levels in humans. Similarly, oral exposure to the putative human-equivalent dose of arsenic species mixture with the same ratios in a common fish meat in Japan increased systolic blood pressure and arsenic levels in fasting serum in mice. CONCLUSION: This interdisciplinary approach suggests that fish-meat ingestion is a potential risk factor for arsenic-mediated hypertension. Because the increased consumption of fish meat is a recent global trend, health risks of the increased ingestion of arsenic via fish meat should be further investigated.

DOI： 10.1093/ehjopen/oead074

Open Access

Dietary carbohydrate and fat intakes and risk of mortality in the Japanese population: the Japan Multi-Institutional Collaborative Cohort Study. Reviewed International journal

Takashi Tamura, Kenji Wakai, Yasufumi Kato, Yudai Tamada, Yoko Kubo, Rieko Okada, Mako Nagayoshi, Asahi Hishida, Nahomi Imaeda, Chiho Goto, Hiroaki Ikezaki, Jun Otonari, Megumi Hara, Keitaro Tanaka, Yohko Nakamura, Miho Kusakabe, Rie Ibusuki, Chihaya Koriyama, Isao Oze, Hidemi Ito, Sadao Suzuki, Hiroko Nakagawa-Senda, Etsuko Ozaki, Daisuke Matsui, Kiyonori Kuriki, Keiko Kondo, Naoyuki Takashima, Takeshi Watanabe, Sakurako Katsuura-Kamano, Keitaro Matsuo

The Journal of nutrition Vol. 153 ( 8 ) page： 2352 - 2368 2023.8

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Previous cohort studies have yielded contradictory findings regarding the associations of dietary carbohydrate and fat intakes with risk of mortality. OBJECTIVES: We examined long-term associations of carbohydrate and fat intakes with mortality. METHODS: In this cohort study, 34,893 men and 46,440 women aged 35-69 years (mean body mass index 23.7 and 22.2 kg/m2, respectively) were followed from the baseline survey (2004-2014) to the end of 2017 or 2018. Intakes of carbohydrate, fat, and total energy were estimated using a food frequency questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for all-cause and cause-specific mortality according to percent energy intakes of carbohydrate and fat. RESULTS: During a mean 8.9 years of follow-up, we identified 2,783 deaths (1,838 men and 945 women). Compared with men who consumed 50%-<55% of energy from carbohydrate, those that consumed <40% carbohydrate energy had a significantly higher risk of all-cause mortality (the multivariable-adjusted HR: 1.59; 95% CI: 1.19-2.12; P-trend = 0.002). Among women with 5 years or longer of follow-up, women with high carbohydrate intake had a higher risk for all-cause mortality; the multivariable-adjusted HR (95% CI) was 1.71 (0.93-3.13) for ≥65% of energy from carbohydrate compared with 50%-<55% (P-trend = 0.005). Men with high fat intake had a higher risk for cancer mortality; the multivariable-adjusted HR (95% CI) for ≥35% was 1.79 (1.11-2.90) compared with 20%-<25%. Fat intake was marginally inversely associated with the risk for all-cause and cancer mortality in women (P-trend = 0.054 and 0.058, respectively). CONCLUSIONS: An unfavorable association with mortality was observed for low carbohydrate intake in men and for high carbohydrate intake in women. High fat intake could be associated with a lower mortality risk in women among Japanese adults with a relatively high carbohydrate intake.

DOI： 10.1016/j.tjnut.2023.05.027

Association of daily physical activity and leisure-time exercise with dysphagia risk in community-dwelling older adults: a cross-sectional study. Reviewed International journal

Tomoko Maehara, Rumi Nishimura, Akari Yoshitake, Mineko Tsukamoto, Yuka Kadomatsu, Yoko Kubo, Rieko Okada, Mako Nagayoshi, Takashi Tamura, Asahi Hishida, Kenji Takeuchi, Kenji Wakai, Mariko Naito

Scientific reports Vol. 13 ( 1 ) page： 10893 - 10893 2023.7

Language：English Publishing type：Research paper (scientific journal) Publisher：Scientific Reports

This study aimed to clarify the association of daily physical activity and leisure-time exercise with the risk of dysphagia in community-dwelling Japanese older adults using a questionnaire-based survey. We analyzed 3070 participants (1657 men, 1413 women; age 66 ± 4 years [mean ± SD]) of the Shizuoka and Daiko studies within the Japanese Multi-Institutional Collaborative Cohort study. We used the Dysphagia Risk Assessment for the Community-dwelling Elderly questionnaire to assess dysphagia risk and the International Physical Activity Questionnaire to assess daily physical activity and leisure-time exercise. Logistic regression analyses were used to evaluate the independent association of the amount of physical activity and leisure-time exercise with dysphagia risk. The proportion of participants with dysphagia risk was 27.5% (n = 844) and the risk was significantly higher in women (29.8%, n = 421) than in men (25.5%, n = 423; P = 0.008). Daily physical activity was not associated with dysphagia risk. A greater amount of leisure-time exercise was associated with lower dysphagia risk (P for trend = 0.003) and individuals in the highest leisure-time exercise quartile had a significantly lower odds ratio (0.68, 95% CI 0.52-0.89) than those in the lowest quartile, even after adjusting for the covariates.

DOI： 10.1038/s41598-023-37605-z

Comparison of the loci associated with HbA1c and blood glucose levels identified by a genome-wide association study in the Japanese population. Reviewed

Takuya Sakashita, Yasuyuki Nakamura, Yoichi Sutoh, Atsushi Shimizu, Tsuyoshi Hachiya, Yayoi Otsuka-Yamasaki, Naoyuki Takashima, Aya Kadota, Katsuyuki Miura, Yoshikuni Kita, Hiroaki Ikezaki, Jun Otonari, Keitaro Tanaka, Chisato Shimanoe, Teruhide Koyama, Isao Watanabe, Sadao Suzuki, Hiroko Nakagawa-Senda, Asahi Hishida, Takashi Tamura, Yasufumi Kato, Rieko Okada, Kiyonori Kuriki, Sakurako Katsuura-Kamano, Takeshi Watanabe, Shiroh Tanoue, Chihaya Koriyama, Isao Oze, Yuriko N Koyanagi, Yohko Nakamura, Miho Kusakabe, Masahiro Nakatochi, Yukihide Momozawa, Kenji Wakai, Keitaro Matsuo

Diabetology international Vol. 14 ( 2 ) page： 188 - 198 2023.4

Language：English Publishing type：Research paper (scientific journal)

AIMS: Hemoglobin A1c (HbA1c) levels are widely employed to diagnose diabetes. However, estimates of the heritability of HbA1c and glucose levels are different. Therefore, we explored HbA1c- and blood glucose-associated loci in a non-diabetic Japanese population. METHODS: We conducted a two-stage genome-wide association study (GWAS) on variants associated with HbA1c and blood glucose levels in a Japanese population. In the initial stage, data of 4911 participants of the Japan Multi-Institutional Collaborative Cohort (J-MICC) were subjected to discovery analysis. In the second stage, two datasets from the Tohoku Medical Megabank project, with 8175 and 40,519 participants, were used for the replication study. Association of the imputed variants with HbA1c and blood glucose levels was determined via linear regression analyses adjusted for age, sex, body mass index (BMI), smoking, and genetic principal components (PC1-PC10). Moreover, we performed a BMI-stratified GWAS on HbA1c levels in the J-MICC. The discovery analysis and BMI-stratified GWAS results were validated with re-analyses of normalized HbA1c levels adjusted for site in addition to the above, and blood glucose adjusted for fasting time as an additional covariate. RESULTS: Genetic variants associated with HbA1c levels were identified in KCNQ1 and TMC6. None of the genetic variants associated with blood glucose levels in the discovery analysis were replicated. Association of rs2299620 in KCNQ1 with HbA1c levels showed heterogeneity between individuals with BMI ≥ 25 kg/m2 and BMI < 25 kg/m2. CONCLUSIONS: The variant rs2299620 in KCNQ1 might affect HbA1c levels differentially based on BMI grouping in the Japanese population. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13340-023-00618-0.

DOI： 10.1007/s13340-023-00618-0

Questionnaire-assessed physical activity among Japanese adults: The J-MICC Study

Saito Yoshinobu, Oguma Yuko, Nakamura Sho, Narimatsu Hiroto, Nakashima Ryoko, Ikezaki Hiroaki, Tanaka Keitaro, Hara Megumi, Tamada Yudai, Nagayoshi Mako, Tamura Takashi, Hishida Asahi, Oze Isao, Taniyama Yukari, Mikami Haruo, Nagase Hiroki, Takezaki Toshiro, Ibusuki Rie, Suzuki Sadao, Otani Takahiro, Koyama Teruhide, Watanabe Isao, Kuriki Kiyonori, Kita Yoshikuni, Takashima Naoyuki, Arisawa Kokichi, Katsuura-Kamano Sakurako, Takeuchi Kenji, Wakai Kenji, J-MICC Study Group

Research in Exercise Epidemiology Vol. 25 ( 1 ) page： 112 - 113 2023.3

Coffee and Metabolic Phenotypes: A Cross-sectional Analysis of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study Reviewed International journal

Takeshi Watanabe, Kokichi Arisawa, Tien Van Nguyen, Masashi Ishizu, Sakurako Katsuura-Kamano, Asahi Hishida, Takashi Tamura, Yasufumi Kato, Rieko Okada, Rie Ibusuki, Chihaya Koriyama, Sadao Suzuki, Takahiro Otani, Teruhide Koyama, Satomi Tomida, Kiyonori Kuriki, Naoyuki Takashima, Naoko Miyagawa, Kenji Wakai, Keitaro Matsuo

Nutrition, Metabolism and Cardiovascular Diseases Vol. 33 ( 3 ) page： 620 - 630 2023.3

Effects of gene-lifestyle interactions on obesity based on a multi-locus risk score: A cross-sectional analysis. Reviewed International journal Open Access

Sho Nakamura, Xuemin Fang, Yoshinobu Saito, Hiroto Narimatsu, Azusa Ota, Hiroaki Ikezaki, Chisato Shimanoe, Keitaro Tanaka, Yoko Kubo, Mineko Tsukamoto, Takashi Tamura, Asahi Hishida, Isao Oze, Yuriko N Koyanagi, Yohko Nakamura, Miho Kusakabe, Toshiro Takezaki, Daisaku Nishimoto, Sadao Suzuki, Takahiro Otani, Nagato Kuriyama, Daisuke Matsui, Kiyonori Kuriki, Aya Kadota, Yasuyuki Nakamura, Kokichi Arisawa, Sakurako Katsuura-Kamano, Masahiro Nakatochi, Yukihide Momozawa, Michiaki Kubo, Kenji Takeuchi, Kenji Wakai

PloS one Vol. 18 ( 2 ) page： e0279169 2023

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The relationship between lifestyle and obesity is a major focus of research. Personalized nutrition, which utilizes evidence from nutrigenomics, such as gene-environment interactions, has been attracting attention in recent years. However, evidence for gene-environment interactions that can inform treatment strategies is lacking, despite some reported interactions involving dietary intake or physical activity. Utilizing gene-lifestyle interactions in practice could aid in optimizing interventions according to genetic risk. METHODS: This study aimed to elucidate the effects of gene-lifestyle interactions on body mass index (BMI). Cross-sectional data from the Japan Multi-Institutional Collaborative Cohort Study were used. Interactions between a multi-locus genetic risk score (GRS), calculated from 76 ancestry-specific single nucleotide polymorphisms, and nutritional intake or physical activity were assessed using a linear mixed-effect model. RESULTS: The mean (standard deviation) BMI and GRS for all participants (n = 12,918) were 22.9 (3.0) kg/m2 and -0.07 (0.16), respectively. The correlation between GRS and BMI was r(12,916) = 0.13 (95% confidence interval [CI] 0.11-0.15, P < 0.001). An interaction between GRS and saturated fatty acid intake was observed (β = -0.11, 95% CI -0.21 to -0.02). An interaction between GRS and n-3 polyunsaturated fatty acids was also observed in the females with normal-weight subgroup (β = -0.12, 95% CI -0.22 to -0.03). CONCLUSION: Our results provide evidence of an interaction effect between GRS and nutritional intake and physical activity. This gene-lifestyle interaction provides a basis for developing prevention or treatment interventions for obesity according to individual genetic predisposition.

DOI： 10.1371/journal.pone.0279169

Open Access

Association between Dietary Patterns and Serum Low Density Lipoprotein Cholesterol in Japanese Women and Men: The Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. Reviewed

Kaori Kitaoka, Katsuyuki Miura, Naoyuki Takashima, Aya Kadota, Akiko Harada, Yasuyuki Nakamura, Yoshikuni Kita, Yuichiro Yano, Takashi Tamura, Mako Nagayoshi, Rieko Okada, Yoko Kubo, Sadao Suzuki, Takeshi Nishiyama, Shiroh Tanoue, Chihaya Koriyama, Kiyonori Kuriki, Kokichi Arisawa, Sakurako Katsuura-Kamano, Yuichiro Nishida, Chisato Shimanoe, Etsuko Ozaki, Daisuke Matsui, Hiroaki Ikezaki, Jun Otonari, Isao Oze, Yuriko N Koyanagi, Yohko Nakamura, Miho Kusakabe, Kenji Wakai, Keitaro Matsuo

Journal of atherosclerosis and thrombosis Vol. 30 ( 10 ) page： 1427 - 1447 2023

Language：English Publishing type：Research paper (scientific journal) Publisher：Japan Atherosclerosis Society

AIMS: The association between dietary patterns and serum low density lipoprotein (LDL) cholesterol would be changing in recent dietary habits in Japan. We investigated the relationship between dietary patterns and serum LDL cholesterol in a large general population. METHODS: From the baseline survey of Japan Multi-Institutional Collaborative Cohort Study between 2005 and 2013, 27,237 participants (13,994 were women) aged 35-69 years were cross-sectionally analyzed. Using a semi-quantitative food frequency questionnaire, five major sex-specific dietary patterns were identified using factor analysis. We assessed serum LDL cholesterol by quintiles of dietary pattern factor score. RESULTS: We identified dietary patterns; "vegetable rich pattern" , "meat and fried food rich pattern" and "high bread and low rice pattern" in women and men; "fish and shellfish rich pattern" and "high confectioneries and low alcohol pattern" in men; "healthy Japanese diet pattern" and "high alcohol and low rice pattern" in women. Serum LDL cholesterol in men was associated with "high bread and low rice pattern" score (Q5 was 4.2 mg/dL higher than Q1, p for trend ＜0.001) and "high confectioneries and low alcohol pattern" scores (Q5 was 9.5 mg/dL higher than Q1, p for trend ＜0.001). In women, serum LDL cholesterol was associated with "high bread and low rice pattern" score (Q5 was 7.1 mg/dL higher than Q1, p for trend ＜0.001). CONCLUSION: Some recent dietary patterns in Japan were associated with serum LDL cholesterol. Serum LDL cholesterol was associated with high bread and low rice pattern in both sex, and high confectioneries and low alcohol pattern in men.

DOI： 10.5551/jat.63675

Irregular sleep and all-cause mortality: A large prospective cohort study. Reviewed International journal

Chie Omichi, Teruhide Koyama, Hiroshi Kadotani, Etsuko Ozaki, Satomi Tomida, Tamami Yoshida, Jun Otonari, Hiroaki Ikezaki, Megumi Hara, Keitaro Tanaka, Takashi Tamura, Mako Nagayoshi, Rieko Okada, Yoko Kubo, Isao Oze, Keitaro Matsuo, Yohko Nakamura, Miho Kusakabe, Rie Ibusuki, Kenichi Shibuya, Sadao Suzuki, Miki Watanabe, Kiyonori Kuriki, Naoyuki Takashima, Aya Kadota, Sakurako Katsuura-Kamano, Kokichi Arisawa, Kenji Takeuchi, Kenji Wakai

Sleep health Vol. 8 ( 6 ) page： 678 - 683 2022.12

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: Previous studies using objective parameters have shown that irregular sleep is associated with the disease incidence, progression, or mortality. This study aimed to determine the association between subjective sleep duration and sleep regularity, with mortality in a large population. METHODS: Participants were from the Japan Multi-Institutional Collaborative Cohort study. We obtained information from each participant on sleep duration, sleep regularity, and demographics and overall lifestyle using self-administered questionnaires. We defined sleep regularity according to participants' subjective assessment of sleep/wake time regularity. Participants (n = 81,382, mean age: 58.1 ± 9.1years, males: 44.2%) were classified into 6 groups according to sleep duration and sleep regularity. Hazard ratios (HR) for time-to-event of death were calculated using the Cox proportional hazards model. RESULTS: The mean follow-up period was 9.1 years and the mean sleep duration was 6.6 h/day. Irregular sleep significantly increased the risk of all-cause mortality in all models compared with regular sleep (HR 1.30, 95% confidence interval; CI, 1.18-1.44), regardless of sleep duration. Multivariable analysis of the 6 groups by sleep pattern (sleep regularity and duration) showed irregular sleep and sleep durations of <6 h/day, 6 to <8 h/day, or ≥8 h/day were associated with a 1.2-1.5-fold increases in mortality, compared to regular sleep and sleep duration of 6 to <8 h/day. CONCLUSIONS: Our study shows an association between sleep irregularity and all-cause mortality in a large Japanese population. Our findings provide further confirmation of the need to consider not only sleep duration, but also the regularity aspect of sleep schedules.

DOI： 10.1016/j.sleh.2022.08.010

Genetic polymorphism of pleiotrophin is associated with pain experience in Japanese adults: Case-control study. Reviewed International journal

Saita K, Sumitani M, Nishizawa D, Tamura T, Ikeda K, Wakai K, Sudo Y, Abe H, Otonari J, Ikezaki H, Takeuchi K, Hishida A, Tanaka K, Shimanoe C, Takezaki T, Ibusuki R, Oze I, Ito H, Ozaki E, Matsui D, Nakamura Y, Kusakabe M, Suzuki S, Nakagawa-Senda H, Arisawa K, Katsuura-Kamano S, Kuriki K, Kita Y, Nakamura Y, Momozawa Y, Uchida K

Medicine Vol. 101 ( 37 ) page： e30580 2022.9

Associations of Genome-Wide Polygenic Risk Score and Risk Factors With Hypertension in a Japanese Population. Reviewed International journal

Ryosuke Fujii, Asahi Hishida, Masahiro Nakatochi, Yoshiki Tsuboi, Koji Suzuki, Takaaki Kondo, Hiroaki Ikezaki, Megumi Hara, Rieko Okada, Takashi Tamura, Ippei Shimoshikiryo, Sadao Suzuki, Teruhide Koyama, Kiyonori Kuriki, Naoyuki Takashima, Kokichi Arisawa, Yukihide Momozawa, Michiaki Kubo, Kenji Takeuchi, Kenji Wakai

Circulation. Genomic and precision medicine Vol. 15 ( 4 ) page： 334 - 341 2022.8

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Although many polygenic risk scores (PRS) for cardiovascular traits have been developed in European populations, it is an urgent task to construct a PRS and to evaluate its ability in non-European populations. We developed a genome-wide PRS for blood pressure in a Japanese population and examined the associations between this PRS and hypertension prevalence. METHODS: We performed a cross-sectional study in 11 252 Japanese individuals who participated in the J-MICC (Japan Multi-Institutional Collaborative Cohort) study. Using publicly available GWAS summary statistics from Biobank Japan, we developed the PRS in the target data (n=7876). With >30 000 single nucleotide polymorphisms, we evaluated PRS performance in the test data (n=3376). Hypertension was defined as systolic blood pressure of 130 mm Hg or more, or diastolic blood pressure of 85 mm Hg or more, or taking an antihypertensive drug. RESULTS: Compared with the middle PRS quintile, the prevalence of hypertension at the top PRS quintile was higher independently from traditional risk factors (odds ratio, 1.73 [95% CI, 1.32-2.27]). The difference of mean systolic blood pressure and diastolic blood pressure between the middle and the top PRS quintile was 4.55 (95% CI, 2.26-6.85) and 2.32 (95% CI, 0.86-3.78) mm Hg, respectively. Subgroups reflecting combinations of Japanese PRS and modifiable lifestyles and factors (smoking, alcohol intake, sedentary time, and obesity) were associated with the prevalence of hypertension. A European-derived PRS was not associated with hypertension in our participants. CONCLUSIONS: A PRS for blood pressure was significantly associated with hypertension and BP traits in a general Japanese population. Our findings also highlighted the importance of a combination of PRS and risk factors for identifying high-risk subgroups.

DOI： 10.1161/CIRCGEN.121.003612

Associations of metabolic syndrome and metabolically unhealthy obesity with cancer mortality: The Japan Multi-Institutional Collaborative Cohort (J-MICC) study. Reviewed International journal

Tien Van Nguyen, Kokichi Arisawa, Sakurako Katsuura-Kamano, Masashi Ishizu, Mako Nagayoshi, Rieko Okada, Asahi Hishida, Takashi Tamura, Megumi Hara, Keitaro Tanaka, Daisaku Nishimoto, Keiichi Shibuya, Teruhide Koyama, Isao Watanabe, Sadao Suzuki, Takeshi Nishiyama, Kiyonori Kuriki, Yasuyuki Nakamura, Yoshino Saito, Hiroaki Ikezaki, Jun Otonari, Yuriko N Koyanagi, Keitaro Matsuo, Haruo Mikami, Miho Kusakabe, Kenji Takeuchi, Kenji Wakai

PloS one Vol. 17 ( 7 ) page： e0269550 2022.7

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: The association between metabolic syndrome (MetS) and the risk of death from cancer is still a controversial issue. The purpose of this study was to examine the associations of MetS and metabolically unhealthy obesity (MUHO) with cancer mortality in a Japanese population. METHODS: We used data from the Japan Multi-Institutional Collaborative Cohort Study. The study population consisted of 28,554 eligible subjects (14,103 men and 14,451 women) aged 35-69 years. MetS was diagnosed based on the criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) and the Japan Society for the Study of Obesity (JASSO), using the body mass index instead of waist circumference. The Cox proportional hazards analysis was used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for total cancer mortality in relation to MetS and its components. Additionally, the associations of obesity and the metabolic health status with cancer mortality were examined. RESULTS: During an average 6.9-year follow-up, there were 192 deaths from cancer. The presence of MetS was significantly correlated with increased total cancer mortality when the JASSO criteria were used (HR = 1.51, 95% CI 1.04-2.21), but not when the NCEP-ATP III criteria were used (HR = 1.09, 95% CI 0.78-1.53). Metabolic risk factors, elevated fasting blood glucose, and MUHO were positively associated with cancer mortality (P <0.05). CONCLUSION: MetS diagnosed using the JASSO criteria and MUHO were associated with an increased risk of total cancer mortality in the Japanese population.

DOI： 10.1371/journal.pone.0269550

OAT10/SLC22A13 Acts as a Renal Urate Re-Absorber: Clinico-Genetic and Functional Analyses With Pharmacological Impacts Reviewed International journal

Toyoda Yu, Kawamura Yusuke, Nakayama Akiyoshi, Morimoto Keito, Shimizu Seiko, Tanahashi Yuki, Tamura Takashi, Kondo Takaaki, Kato Yasufumi, Ichida Kimiyoshi, Suzuki Hiroshi, Shinomiya Nariyoshi, Kobayashi Yasushi, Takada Tappei, Matsuo Hirotaka

FRONTIERS IN PHARMACOLOGY Vol. 13 page： 842717 2022.4

Language：English Publishing type：Research paper (scientific journal) Publisher：Frontiers in Pharmacology

Dysfunctional missense variant of organic anion transporter 10 (OAT10/SLC22A13), rs117371763 (c.1129C>T; p.R377C), is associated with a lower susceptibility to gout. OAT10 is a urate transporter; however, its physiological role in urate handling remains unclear. We hypothesized that OAT10 could be a renal urate re-absorber that will be a new molecular target of urate-lowering therapy like urate transporter 1 (URAT1, a physiologically-important well-known renal urate re-absorber) and aimed to examine the effect of OAT10 dysfunction on renal urate handling. For this purpose, we conducted quantitative trait locus analyses of serum urate and fractional excretion of uric acid (FEUA) using samples obtained from 4,521 Japanese males. Moreover, we performed immunohistochemical and functional analyses to assess the molecular properties of OAT10 as a renal urate transporter and evaluated its potential interaction with urate-lowering drugs. Clinico-genetic analyses revealed that carriers with the dysfunctional OAT10 variant exhibited significantly lower serum urate levels and higher FEUA values than the non-carriers, indicating that dysfunction of OAT10 increases renal urate excretion. Given the results of functional assays and immunohistochemical analysis demonstrating the expression of human OAT10 in the apical side of renal proximal tubular cells, our data indicate that OAT10 is involved in the renal urate reabsorption in renal proximal tubules from urine. Additionally, we found that renal OAT10 inhibition might be involved in the urate-lowering effect of losartan and lesinurad which exhibit uricosuric effects; indeed, losartan, an approved drug, inhibits OAT10 more strongly than URAT1. Accordingly, OAT10 can be a novel potential molecular target for urate-lowering therapy.

DOI： 10.3389/fphar.2022.842717

The association of reproductive history with hypertension and obesity according to menopausal status: the J-MICC Study. Reviewed International journal

Mizuki Ohashi, Katsuyuki Miura, Naoyuki Takashima, Aya Kadota, Yoshino Saito, Shunichiro Tsuji, Takashi Murakami, Yuka Kadomatsu, Mako Nagayoshi, Megumi Hara, Keitaro Tanaka, Takashi Tamura, Asahi Hishida, Toshiro Takezaki, Ippei Shimoshikiryo, Etsuko Ozaki, Isao Watanabe, Sadao Suzuki, Miki Watanabe, Kiyonori Kuriki, Kokichi Arisawa, Sakurako Katsuura-Kamano, Sho Yamasaki, Hiroaki Ikezaki, Isao Oze, Yuriko N Koyanagi, Haruo Mikami, Yohko Nakamura, Kenji Takeuchi, Yoshikuni Kita, Kenji Wakai

Hypertension research : official journal of the Japanese Society of Hypertension Vol. 45 ( 4 ) page： 708 - 714 2022.4

Language：English Publishing type：Research paper (scientific journal)

Previous studies have reported that the number of pregnancies and childbirths affected the risk of cardiovascular diseases (CVDs). However, the influence of reproductive history on hypertension and obesity, which are important risk factors for CVDs, is still unclear. Moreover, this association may vary depending on menopausal status. We evaluated the association of reproductive history with hypertension and obesity using a large cross-sectional dataset from the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study). At the baseline survey, physical data, blood samples, and self-reported health questionnaires were collected. Participants with insufficient data were excluded, and 24,558 women from eight study regions were included in this study. Logistic regression analysis was conducted to evaluate the association of reproductive history with hypertension and obesity using multivariable-adjusted odds ratios. In premenopausal women, childbirth showed a generally protective effect on hypertension but not on obesity. In postmenopausal women, childbirth was positively associated with obesity and hypertension but not with hypertension after adjusting for BMI. In conclusion, reproductive history was associated with hypertension and obesity in a large Japanese population, and this association differed between premenopausal and postmenopausal women.

DOI： 10.1038/s41440-021-00820-0

Investigation of miRNA expression profiles using cohort samples reveals potential early detectability of colorectal cancers by serum miR-26a-5p before clinical diagnosis. Reviewed International journal

Asahi Hishida, Hiroya Yamada, Yoshitaka Ando, Yoshinaga Okugawa, Manabu Shiozawa, Yohei Miyagi, Yataro Daigo, Yuji Toiyama, Yumiko Shirai, Koji Tanaka, Yoko Kubo, Rieko Okada, Mako Nagayoshi, Takashi Tamura, Atsuyoshi Mori, Takaaki Kondo, Nobuyuki Hamajima, Kenji Takeuchi, Kenji Wakai

Oncology letters Vol. 23 ( 3 ) page： 87 - 87 2022.3

Language：English Publishing type：Research paper (scientific journal)

Previous studies have investigated the usefulness of microRNA (miRNA/miR) expression data for the early detection of colorectal cancer (CRC). However, limited data are available regarding miRNAs that detect CRC before clinical diagnoses. Accordingly, the present study investigated the early detectability of CRC by miRNAs using the preserved serum samples of the cohort participants affected with CRC within 2 years of study enrollment. First, the significant miRNAs were revealed using clinical CRC samples for a (seven early CRCs and seven controls) microarray analysis based on significance analysis of microarrays. Next, replicability was verified by reverse transcription-quantitative (RT-q)PCR (eight early CRCs and eight controls, together with 12 CRCs and 12 controls). Finally, early detectability was tested using the cohort samples of Japan Multi-Institutional Collaborative Cohort Study (17 CRCs and 17 controls) to reveal how a certain number of patients developed CRC within 2 years after participation. In the discovery phase, miRNA expression measurements were conducted using a 3D-Gene Human miRNA Oligo Chip for 2,555 miRNAs, and RT-qPCR analyses were performed to validate the replicability. In the first validation set with eight CRCs with early clinical stage and eight age- and gender-matched controls, miR-26a-5p and miR-223-3p demonstrated the highest diagnostic accuracy of area under the curve (AUC)=1.000 (sensitivity and specificity 100%). In an examination of the predictability of CRC incidence using pre-clinical cohort samples, miR-26a-5p demonstrated good predictability of advanced CRC incidence with an AUC of 0.840. Overall, the present study revealed serum miR-26a-5p as a potential early detection marker for CRC.

DOI： 10.3892/ol.2022.13207

A genome-wide association study on adherence to low-carbohydrate diets in Japanese. Reviewed International journal

Yasuyuki Nakamura, Takashi Tamura, Akira Narita, Atsushi Shimizu, Yoichi Sutoh, Naoyuki Takashima, Kenji Matsui, Naoko Miyagawa, Aya Kadota, Katsuyuki Miura, Jun Otonari, Hiroaki Ikezaki, Asahi Hishida, Mako Nagayoshi, Rieko Okada, Yoko Kubo, Keitaro Tanaka, Chisato Shimanoe, Rie Ibusuki, Daisaku Nishimoto, Isao Oze, Hidemi Ito, Etsuko Ozaki, Daisuke Matsui, Haruo Mikami, Miho Kusakabe, Sadao Suzuki, Miki Watanabe, Kokichi Arisawa, Sakurako Katsuura-Kamano, Kiyonori Kuriki, Masahiro Nakatochi, Yukihide Momozawa, Michiaki Kubo, Kenji Takeuchi, Kenji Wakai

European journal of clinical nutrition 2022.2

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND/OBJECTIVES: Low-carbohydrate diets (LCD) are useful for weight reduction, and 50-55% carbohydrate consumption is associated with minimal risk. Genetic differences were related to nutritional consumption, food preferences, and dietary patterns, but whether particular genetic differences in individuals influence LCD adherence is unknown. SUBJECTS/METHODS: We conducted a GWAS on adherence to LCD utilizing 14,076 participants from the Japan Multi-Institutional Collaborative Cohort study. We used a previously validated semiquantitative food frequency questionnaire to estimate food consumption. Association of the imputed variants with the LCD score by Halton et al. we used linear regression analysis adjusting for sex, age, total dietary energy consumption, and components 1 to 10 by principal component analysis. We repeated the analysis with adjustment for alcohol consumption (g/day) in addition to the above-described variables. RESULTS: Men and women combined analysis without adjustment for alcohol consumption; we found 395 variants on chromosome 12 associated with the LCD score having P values <5 × 10-8. A conditional analysis with the addition of the dosage data of rs671 on chromosome 12 as a covariate, P values for all 395 SNPs on chromosome 12 turned out to be insignificant. In the analysis with additional adjustment for alcohol consumption, we did not identify any SNPs associated with the LCD score. CONCLUSION: We found rs671 was inversely associated with adherence to LCD, but that was strongly confounded by alcohol consumption.

DOI： 10.1038/s41430-022-01090-w

Associations of breastfeeding history with metabolic syndrome and cardiovascular risk factors in community-dwelling parous women: The Japan Multi-Institutional Collaborative Cohort Study. Reviewed International journal

Takashi Matsunaga, Yuka Kadomatsu, Mineko Tsukamoto, Yoko Kubo, Rieko Okada, Mako Nagayoshi, Takashi Tamura, Asahi Hishida, Toshiro Takezaki, Ippei Shimoshikiryo, Sadao Suzuki, Hiroko Nakagawa, Naoyuki Takashima, Yoshino Saito, Kiyonori Kuriki, Kokichi Arisawa, Sakurako Katsuura-Kamano, Nagato Kuriyama, Daisuke Matsui, Haruo Mikami, Yohko Nakamura, Isao Oze, Hidemi Ito, Masayuki Murata, Hiroaki Ikezaki, Yuichiro Nishida, Chisato Shimanoe, Kenji Takeuchi, Kenji Wakai

PloS one Vol. 17 ( 1 ) page： e0262252 2022.1

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: The aim of the present study was to investigate the associations between breastfeeding and the prevalence of metabolic syndrome in community-dwelling parous women and to clarify whether the associations depend on age. METHODS: The present cross-sectional study included 11,118 women, aged 35-69 years. Participants' longest breastfeeding duration for one child and their number of breastfed children were assessed using a self-administered questionnaire, and their total breastfeeding duration was approximated as a product of the number of breastfed children and the longest breastfeeding duration. The longest and the total breastfeeding durations were categorized into none and tertiles above 0 months. Metabolic syndrome and cardiovascular risk factors (obesity, hypertension, dyslipidemia, and hyperglycemia) were defined as primary and secondary outcomes, respectively. Associations between breastfeeding history and metabolic syndrome or each cardiovascular risk factor were assessed using multivariable unconditional logistic regression analysis. RESULTS: Among a total of 11,118 women, 10,432 (93.8%) had ever breastfed, and 1,236 (11.1%) had metabolic syndrome. In participants aged <55 years, an inverse dose-response relationship was found between the number of breastfed children and the prevalence of metabolic syndrome; multivariable-adjusted odds ratios for 1, 2, 3, and ≥4 breastfed children were 0.60 (95% confidence interval [CI]: 0.31 to 1.17), 0.50 (95% CI: 0.29 to 0.87), 0.44 (95% CI: 0.24 to 0.84), and 0.35 (95% CI: 0.14 to 0.89), respectively. The longest and total breastfeeding durations of longer than 0 months were also associated with lower odds of metabolic syndrome relative to no breastfeeding history in participants aged <55 years. In contrast, all measures of breastfeeding history were not significantly associated with metabolic syndrome and cardiovascular risk factors in participants aged ≥55 years old. CONCLUSIONS: Breastfeeding history may be related to lower prevalence of metabolic syndrome in middle-aged parous women.

DOI： 10.1371/journal.pone.0262252

Association of perceived stress and coping strategies with the renal function in middle-aged and older Japanese men and women. Reviewed International journal

Kayoko Koga, Megumi Hara, Chisato Shimanoe, Yuichiro Nishida, Takuma Furukawa, Chiharu Iwasaka, Keitaro Tanaka, Jun Otonari, Hiroaki Ikezaki, Yoko Kubo, Yasufumi Kato, Takashi Tamura, Asahi Hishida, Keitaro Matsuo, Hidemi Ito, Yohko Nakamura, Miho Kusakabe, Daisaku Nishimoto, Keiichi Shibuya, Sadao Suzuki, Miki Watanabe, Etsuko Ozaki, Daisuke Matsui, Kiyonori Kuriki, Naoyuki Takashima, Aya Kadota, Kokichi Arisawa, Sakurako Katsuura-Kamano, Kenji Takeuchi, Kenji Wakai

Scientific reports Vol. 12 ( 1 ) page： 291 - 291 2022.1

Language：English Publishing type：Research paper (scientific journal)

Elucidating the risk factors for chronic kidney disease is important for preventing end-stage renal disease and reducing mortality. However, little is known about the roles of psychosocial stress and stress coping behaviors in deterioration of the renal function, as measured by the estimated glomerular filtration rate (eGFR). This cross-sectional study of middle-aged and older Japanese men (n = 31,703) and women (n = 38,939) investigated whether perceived stress and coping strategies (emotional expression, emotional support seeking, positive reappraisal, problem solving, and disengagement) were related to the eGFR, with mutual interactions. In multiple linear regression analyses adjusted for age, area, lifestyle factors, and psychosocial variables, we found a significant inverse association between perceived stress and the eGFR in men (Ptrend = 0.02), but not women. This male-specific inverse association was slightly attenuated after adjustment for the history of hypertension and diabetes and was more evident in lower levels of emotional expression (Pinteraction = 0.003). Unexpectedly, problem solving in men (Ptrend < 0.001) and positive reappraisal in women (Ptrend = 0.002) also showed an inverse association with the eGFR. Perceived stress may affect the eGFR, partly through the development of hypertension and diabetes. The unexpected findings regarding coping strategies require the clarification of the underlying mechanisms, including the hormonal and immunological aspects.

DOI： 10.1038/s41598-021-04324-2

Alcohol intake and stomach cancer risk in Japan: A pooled analysis of six cohort studies. Reviewed International journal

Takashi Tamura, Kenji Wakai, Yingsong Lin, Akiko Tamakoshi, Mai Utada, Kotaro Ozasa, Yumi Sugawara, Ichiro Tsuji, Ayami Ono, Norie Sawada, Shoichiro Tsugane, Hidemi Ito, Chisato Nagata, Tetsuhisa Kitamura, Mariko Naito, Keitaro Tanaka, Taichi Shimazu, Tetsuya Mizoue, Keitaro Matsuo, Manami Inoue

Cancer science Vol. 113 ( 1 ) page： 261 - 276 2022.1

Language：English Publishing type：Research paper (scientific journal)

The association between alcohol intake and stomach cancer risk remains controversial. We undertook a pooled analysis of data from six large-scale Japanese cohort studies with 256 478 participants on this topic. Alcohol intake as ethanol was estimated using a validated questionnaire. The participants were followed for incidence of stomach cancer. We calculated study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for stomach cancer according to alcohol intake using a Cox regression model. Summary HRs were estimated by pooling the study-specific HRs using a random-effects model. During 4 265 551 person-years of follow-up, 8586 stomach cancer cases were identified. In men, the multivariate-adjusted HRs (95% CIs) of stomach cancer were 1.00 (0.87-1.15) for occasional drinkers, and 1.00 (0.91-1.11) for <23 g/d, 1.09 (1.01-1.18) for 23 to <46 g/d, 1.18 (1.09-1.29) for 46 to <69 g/d, 1.21 (1.05-1.39) for 69 to <92 g/d, and 1.29 (1.11-1.51) for ≥92 g/d ethanol in regular drinkers compared with nondrinkers. In women, the multivariate-adjusted HRs were 0.93 (0.80-1.08) for occasional drinkers, and 0.85 (0.74-0.99) for <23 g/d, and 1.22 (0.98-1.53) for ≥23 g/d in regular drinkers compared with nondrinkers. The HRs for proximal and distal cancer in drinkers vs nondrinkers were 1.69 (1.15-2.47) and 1.24 (0.99-1.55) for ≥92 g/d in men, and 1.60 (0.76-3.37) and 1.18 (0.88-1.57) for ≥23 g/d in women, respectively. Alcohol intake increased stomach cancer risk in men, and heavy drinkers showed a greater point estimate of risk for proximal cancer than for distal cancer.

DOI： 10.1111/cas.15172

Effect of the interaction between physical activity and estimated macronutrient intake on HbA1c: population-based cross-sectional and longitudinal studies. Reviewed International journal

Takuma Furukawa, Yuichiro Nishida, Megumi Hara, Chisato Shimanoe, Kayoko Koga, Chiharu Iwasaka, Yasuki Higaki, Keitaro Tanaka, Ryoko Nakashima, Hiroaki Ikezaki, Asahi Hishida, Takashi Tamura, Yasufumi Kato, Yudai Tamada, Keitaro Matsuo, Hidemi Ito, Haruo Mikami, Miho Kusakabe, Rie Ibusuki, Keiichi Shibuya, Sadao Suzuki, Hiroko Nakagawa-Senda, Etsuko Ozaki, Daisuke Matsui, Kiyonori Kuriki, Yasuyuki Nakamura, Aya Kadota, Kokichi Arisawa, Sakurako Katsuura-Kamano, Kenji Takeuchi, Kenji Wakai

BMJ open diabetes research & care Vol. 10 ( 1 ) 2022.1

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Healthy diet and physical activity (PA) are essential for preventing type 2 diabetes, particularly, a combination of diet and PA. However, reports on interaction between PA and diet, especially from large epidemiological studies, are limited. We investigated the effect of interaction between PA and macronutrient intake on hemoglobin A1c (HbA1c) levels in the general population. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional study of 55 469 men and women without diabetes who participated in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. A self-administered questionnaire ascertained PA and macronutrient intake (carbohydrate, fat, and protein). Multiple linear regression analyses were performed to adjust for confounding variables and examine the interactions. In addition, we conducted a longitudinal study during a 5-year period within a subcohort (n=6881) with accelerometer-assessed PA data. RESULTS: Overall, PA had a weak inverse association (β=-0.00033, p=0.049) and carbohydrate intake had a strong positive association (β=0.00393, p<0.001) with HbA1c. We observed a tendency of interactions between PA and carbohydrate or fat intake, but not protein intake, on HbA1c levels after adjusting for age, sex, study area, total energy intake, alcohol consumption, smoking, and medication for hypertension or hypercholesterolemia (Pinteraction=0.054, 0.006, and 0.156, respectively). The inverse associations between PA and HbA1c level were more evident in participants with high-carbohydrate (or low-fat) intake than in participants with low-carbohydrate (or high-fat) intake. Although further adjustment for body mass index slightly attenuated the above interactions (Pinteraction=0.098 for carbohydrate and 0.068 for fat), the associations between PA and HbA1c level in stratified analyses remained unchanged. Similar associations and interactions were reproduced in the longitudinal study. CONCLUSIONS: The present results suggest that the effect of PA on HbA1c levels is modified by intake of macronutrient composition.

DOI： 10.1136/bmjdrc-2021-002479

Association of skipping breakfast and short sleep duration with the prevalence of metabolic syndrome in the general Japanese population: Baseline data from the Japan Multi-Institutional Collaborative cohort study. Reviewed International journal

Sakurako Katsuura-Kamano, Kokichi Arisawa, Hirokazu Uemura, Tien Van Nguyen, Toshiro Takezaki, Rie Ibusuki, Sadao Suzuki, Takahiro Otani, Rieko Okada, Yoko Kubo, Takashi Tamura, Asahi Hishida, Teruhide Koyama, Daisuke Matsui, Kiyonori Kuriki, Naoyuki Takashima, Naoko Miyagawa, Hiroaki Ikezaki, Yuji Matsumoto, Yuichiro Nishida, Chisato Shimanoe, Isao Oze, Keitaro Matsuo, Haruo Mikami, Miho Kusakabe, Kenji Takeuchi, Kenji Wakai

Preventive medicine reports Vol. 24 page： 101613 - 101613 2021.12

Language：English Publishing type：Research paper (scientific journal)

The purpose of the study was to investigate sex-specific associations of skipping breakfast and short sleep duration with metabolic syndrome (MetS) and their interaction. We analyzed baseline data of 14,907 men and 14,873 women aged 35-69 years, who participated in the Japan Multi-Institutional Collaborative Cohort Study from 2005. MetS was diagnosed using a modification of the National Cholesterol Education Program Adult Treatment Panel III revised definition (NCEP-R 2005), using body mass index instead of waist circumference. Breakfast consumption was classified into two categories: ≥6 days/week (consumers) or <6 days/week (skippers). Sleep duration was classified into three categories: <6h, 6 to <8 h, and ≥8 h/day. Multivariate logistic regression analysis was performed to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) and examine the presence of interaction. In men, skipping breakfast and short sleep duration were independently associated with an increased prevalence of MetS (OR 1.26, 95%CI 1.12-1.42 and OR 1.28, 95%CI 1.12-1.45, respectively), obesity, and components of MetS. However, no significant interaction was observed between skipping breakfast and short sleep duration. In women, skipping breakfast and short sleep duration were associated with an increased prevalence of obesity, but not with MetS. These findings indicate that breakfast consumption and moderate sleep duration may be associated with a lower risk of MetS, particularly in men.

DOI： 10.1016/j.pmedr.2021.101613

Moderate-to-vigorous physical activity and sedentary behavior are independently associated with renal function: a cross-sectional study. Reviewed

Megumi Hara, Yuichiro Nishida, Keitaro Tanaka, Chisato Shimanoe, Kayoko Koga, Takuma Furukawa, Yasuki Higaki, Koichi Shinchi, Hiroaki Ikezaki, Masayuki Murata, Kenji Takeuchi, Takashi Tamura, Asahi Hishida, Mineko Tsukamoto, Yuka Kadomatsu, Keitaro Matsuo, Isao Oze, Mikami Haruo, Kusakabe Miho, Toshiro Takezaki, Rie Ibusuki, Sadao Suzuki, Hiroko Nakagawa-Senda, Daisuke Matsui, Teruhide Koyama, Kiyonori Kuriki, Naoyuki Takashima, Yasuyuki Nakamura, Kokichi Arisawa, Sakurako Katsuura-Kamano, Kenji Wakai

Journal of epidemiology Vol. advpub ( 0 ) 2021.10

Language：English Publishing type：Research paper (scientific journal) Publisher：Japan Epidemiological Association

BACKGROUND: Little is known about whether insufficient moderate-to-vigorous physical activity (MVPA) and longer sedentary behavior (SB) are independently associated with estimated glomerular filtration rate (eGFR) and CKD, whether they interact with known risk factors for CKD, and the effect of replacing sedentary time with an equivalent duration of physical activity on kidney function. METHODS: We examined the cross-sectional association of MVPA and SB with eGFR and CKD in 66,603 Japanese cohort study in 14 areas from 2004 to 2013. MVPA and SB were estimated using a self-reported questionnaire, and CKD was defined as eGFR<60 mL/min/1.73 m2. Multiple linear regression analyses, logistic regression analyses, and an isotemporal substitution model were applied. RESULTS: After adjusting for potential confounders, higher MVPA and longer SB were independently associated with higher eGFR (Pfor trend MVPA<0.0001) and lower eGFR (Pfor trend SB<0.0001), and a lower odds ratio (OR) of CKD (adjusted OR of MVPA≥20 MET·h/day: 0.76 [95%CI: 0.68-0.85] compared to MVPA<5 MET·h/day) and a higher OR of CKD (adjusted OR of SB≥16 h/day: 1.81 [95%CI: 1.52-2.15] compared to SB<7 h/day), respectively. The negative association between MVPA and CKD was stronger in men, and significant interactions between sex and MVPA were detected. Replacing 1 hour of SB with 1 hour of physical activity was associated with about 3 to 4% lower OR of CKD. CONCLUSIONS: These findings indicate that replacing SB with physical activity may benefit kidney function, especially in men, adding to the possible evidence on CKD prevention.

DOI： 10.2188/jea.JE20210155

A genome-wide association study on meat consumption in a Japanese population: the Japan Multi-Institutional Collaborative Cohort study. Reviewed International journal

Yasuyuki Nakamura, Akira Narita, Yoichi Sutoh, Nahomi Imaeda, Chiho Goto, Kenji Matsui, Naoyuki Takashima, Aya Kadota, Katsuyuki Miura, Masahiro Nakatochi, Takashi Tamura, Asahi Hishida, Ryoko Nakashima, Hiroaki Ikezaki, Megumi Hara, Yuichiro Nishida, Toshiro Takezaki, Rie Ibusuki, Isao Oze, Hidemi Ito, Nagato Kuriyama, Etsuko Ozaki, Haruo Mikami, Miho Kusakabe, Hiroko Nakagawa-Senda, Sadao Suzuki, Sakurako Katsuura-Kamano, Kokichi Arisawa, Kiyonori Kuriki, Yukihide Momozawa, Michiaki Kubo, Kenji Takeuchi, Yoshikuni Kita, Kenji Wakai

Journal of nutritional science Vol. 10 page： e61 2021.10

Language：English Publishing type：Research paper (scientific journal)

Recent genome-wide association studies (GWAS) on the dietary habits of the Japanese population have shown that an effect rs671 allele was inversely associated with fish consumption, whereas it was directly associated with coffee consumption. Although meat is a major source of protein and fat in the diet, whether genetic factors that influence meat-eating habits in healthy populations are unknown. This study aimed to conduct a GWAS to find genetic variations that affect meat consumption in a Japanese population. We analysed GWAS data using 14 076 participants from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study. We used a semi-quantitative food frequency questionnaire to estimate food intake that was validated previously. Association of the imputed variants with total meat consumption per 1000 kcal energy was performed by linear regression analysis with adjustments for age, sex, and principal component analysis components 1-10. We found that no genetic variant, including rs671, was associated with meat consumption. The previously reported single nucleotide polymorphisms that were associated with meat consumption in samples of European ancestry could not be replicated in our J-MICC data. In conclusion, significant genetic factors that affect meat consumption were not observed in a Japanese population.

DOI： 10.1017/jns.2021.49

Sex-specific Relationship between Stress Coping Strategies and All-Cause Mortality: Japan Multi-Institutional Collaborative Cohort Study. Reviewed

Nagayoshi M, Takeuchi K, Tamada Y, Yasufumi K, Kubo Y, Okada R, Tamura T, Hishida A, Otonari J, Ikezaki H, Nishida Y, Shimanoe C, Koyanagi YN, Matsuo K, Haruo M, Miho K, Nishimoto D, Shibuya K, Suzuki S, Nishiyama T, Ozaki E, Watanabe I, Kuriki K, Takashima N, Kadota A, Arisawa K, Katsuura-Kamano S, Wakai K

Journal of epidemiology 2021.9

Language：English Publishing type：Research paper (scientific journal) Publisher：日本疫学会

Background: Stress coping strategies are related to health outcomes. However, there is no clear evidence for sex differences between stress-coping strategies and mortality. We investigated the relationship between all-cause mortality and stress-coping strategies, focusing on sex differences among Japanese adults.Methods: A total of 79,580 individuals aged 35–69 years participated in the Japan Multi-Institutional Collaborative Cohort Study between 2004 and 2014 and were followed up for mortality. The frequency of use of the five coping strategies was assessed using a questionnaire. Sex-specific, multivariable-adjusted hazard ratios (HRs) for using each coping strategy "sometimes," and "often/very often" (versus "very few" use) were computed for all-cause mortality. Furthermore, relationships were analyzed in specific follow-up periods when the proportion assumption was violated.Results: During the follow-up (median: 8.5 years), 1,861 mortalities were recorded. In women, three coping strategies were related to lower total mortality. The HRs (95% confidence intervals) for "sometimes" were 0.81 (0.67–0.97) for emotional expression, 0.79 (0.66–0.95) for emotional support-seeking, and 0.80 (0.66–0.98) for disengagement. Men who "sometimes" used emotional expression and sometimes or often used problem-solving and positive reappraisal had a 15–41% lower HRs for all-cause mortality. However, those relationships were dependent on the follow-up period. There was evidence that sex modified the relationships between emotional support-seeking and all-cause mortality (p for interaction = 0.03).Conclusions: In a large Japanese population, selected coping strategies were associated with all-cause mortality. The relationship of emotional support-seeking was different between men and women.

DOI： 10.2188/jea.JE20210220

Population-Based Impact of Smoking, Drinking, and Genetic Factors on HDL-Cholesterol Levels in J-MICC Study Participants. Reviewed

Nindita Y, Nakatochi M, Ibusuki R, Shimoshikiryo I, Nishimoto D, Shimatani K, Takezaki T, Ikezaki H, Murata M, Hara M, Nishida Y, Tamura T, Hishida A, Nagayoshi M, Okada R, Matsuo K, Ito H, Mikami H, Nakamura Y, Otani T, Suzuki S, Koyama T, Ozaki E, Kuriki K, Takashima N, Miyagawa N, Arisawa K, Katsuura-Kamao S, Momozawa Y, Kubo M, Takeuchi K, Wakai K

Journal of epidemiology 2021.8

Language：English Publishing type：Research paper (scientific journal) Publisher：日本疫学会

Background: Environmental and genetic factors are suggested to exhibit factor-based association with HDL-cholesterol (HDL-C) levels. However, the population-based effects of environmental and genetic factors have not been compared clearly. We conducted a cross-sectional study using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study to evaluate the population-based impact of smoking, drinking, and genetic factors on low HDL-C.Methods: Data from 11,498 men and women aged 35-69 years were collected for a genome-wide association study (GWAS). Sixty-five HDL-C-related SNPs with genome-wide significance (P < 5 × 10-8) were selected from the GWAS catalog, and seven representative SNPs were defined, and the population-based impact was estimated using population attributable fraction (PAF).Results: We found that smoking, drinking, daily activity, habitual exercise, egg intake, BMI, age, sex and the SNPs CETP rs3764261, APOA5 rs662799, LIPC rs1800588, LPL rs328, ABCA1 rs2575876, LIPG rs3786247, and APOE rs429358 were associated with HDL-C levels. The gene-environmental interactions on smoking and drinking were not statistically significant. The PAF for low HDL-C was the highest in men (63.2%) and in rs3764261 (31.5%) of the genetic factors, and the PAFs of smoking and drinking were 23.1% and 41.8%, respectively.Conclusions: The present study showed that the population-based impact of genomic factor CETP rs3764261 for low HDL-C was higher than that of smoking and lower than that of drinking.

DOI： 10.2188/jea.JE20210142

A Proposal for Practical Diagnosis of Renal Hypouricemia: Evidenced from Genetic Studies of Nonfunctional Variants of URAT1/SLC22A12 among 30,685 Japanese Individuals Reviewed International journal

Kawamura Yusuke, Nakayama Akiyoshi, Shimizu Seiko, Toyoda Yu, Nishida Yuichiro, Hishida Asahi, Katsuura-Kamano Sakurako, Shibuya Kenichi, Tamura Takashi, Kawaguchi Makoto, Suzuki Satoko, Iwasawa Satoko, Nakashima Hiroshi, Ibusuki Rie, Uemura Hirokazu, Hara Megumi, Takeuchi Kenji, Takada Tappei, Tsunoda Masashi, Arisawa Kokichi, Takezaki Toshiro, Tanaka Keitaro, Ichida Kimiyoshi, Wakai Kenji, Shinomiya Nariyoshi, Matsuo Hirotaka

BIOMEDICINES Vol. 9 ( 8 ) 2021.8

Language：English Publishing type：Research paper (scientific journal) Publisher：Biomedicines

Background: Renal hypouricemia (RHUC) is characterized by a low serum uric acid (SUA) level and high fractional excretion of uric acid (FEUA). Further studies on FEUA in hypouricemic individuals are needed for a more accurate diagnosis of RHUC. Methods: In 30,685 Japanese health-examination participants, we genotyped the two most common nonfunctional variants of URAT1 (NFV-URAT1), W258X (rs121907892) and R90H (rs121907896), in 1040 hypouricemic individuals (SUA ≤ 3.0 mg/dL) and 2240 individuals with FEUA data. The effects of NFV-URAT1 on FEUA and SUA were also investigated using linear and multiple regression analyses. Results: Frequency of hypouricemic individuals (SUA ≤ 3.0 mg/dL) was 0.97% (male) and 6.94% (female) among 30,685 participants. High frequencies of those having at least one allele of NFV-URAT1 were ob-served in 1040 hypouricemic individuals. Furthermore, NFV-URAT1 significantly increased FEUA and decreased SUA, enabling FEUA and SUA levels to be estimated. Conversely, FEUA and SUA data of hypouricemic individuals are revealed to be useful to predict the number of NFV-URAT1. Conclusions: Our findings reveal that specific patterns of FEUA and SUA data assist with predicting the number of nonfunctional variants of causative genes for RHUC, and can also be useful for practical diagnosis of RHUC even before genetic tests.

DOI： 10.3390/biomedicines9081012

A genome-wide association study in Japanese identified one variant associated with a preference for a Japanese dietary pattern Reviewed International journal

Suzuki Harumitsu, Nakamura Yasuyuki, Matsuo Keitaro, Imaeda Nahomi, Goto Chiho, Narita Akira, Shimizu Atsushi, Takashima Naoyuki, Matsui Kenji, Miura Katsuyuki, Nakatochi Masahiro, Hishida Asahi, Tamura Takashi, Kadomatsu Yuka, Okada Rieko, Nishida Yuichiro, Shimanoe Chisato, Nishimoto Daisaku, Takezaki Toshiro, Oze Isao, Ito Hidemi, Ikezaki Hiroaki, Murata Masayuki, Matsui Daisuke, Ozaki Etsuko, Mikami Haruo, Nakamura Yohko, Suzuki Sadao, Watanabe Miki, Arisawa Kokichi, Uemura Hirokazu, Kuriki Kiyonori, Momozawa Yukihide, Kubo Michiaki, Kita Yoshikuni, Takeuchi Kenji, Wakai Kenji

EUROPEAN JOURNAL OF CLINICAL NUTRITION Vol. 75 ( 6 ) page： 937 - 945 2021.6

Language：English Publishing type：Research paper (scientific journal) Publisher：European Journal of Clinical Nutrition

Background/Objectives: Individual eating habits may be influenced by genetic factors, in addition to environmental factors. Previous studies suggested that adherence to Japanese food patterns was associated with a decreased risk of all-cause and cardiovascular disease mortality. We conducted a genome-wide association study (GWAS) in a Japanese population to find genetic variations that affect adherence to a Japanese food pattern. Subjects/Methods: We analyzed GWAS data using 14,079 participants from the Japan Multi-Institutional Collaborative Cohort study. We made a Japanese food score based on six food groups. Association of the imputed variants with the Japanese food score was performed by linear regression analysis with adjustments for age, sex, total energy intake, alcohol intake (g/day), and principal components 1–10 omitting variants in the major histocompatibility region. Results: We found one SNP in the 14q11.2 locus that was significantly associated with the Japanese food score with P values <5 × 10−8. Functional annotation revealed that the expression levels of two genes (BCL2L2, SLC22A17) were significantly inversely associated with this SNP. These genes are known to be related to olfaction and obesity. Conclusion: We found a new SNP that was associated with the Japanese food score in a Japanese population. This SNP is inversely associated with genes link to olfaction and obesity.

DOI： 10.1038/s41430-020-00823-z

Association of self-reported moderate vegetable juice intake with small decline in kidney function in a five-year prospective study Reviewed International journal

Fujii Ryosuke, Kondo Takaaki, Tsukamoto Mineko, Kawai Sayo, Sasakabe Tae, Naito Mariko, Kubo Yoko, Okada Rieko, Tamura Takashi, Hishida Asahi, Ueyama Jun, Hayashi Yumi, Ohnishi Joji, Hamajima Nobuyuki, Takeuchi Kenji, Wakai Kenji

NUTRITION Vol. 84 page： 111114 2021.4

Language：English Publishing type：Research paper (scientific journal) Publisher：Nutrition

Objectives: Although consumption of vegetable and 100% fruit juices are an acceptable alternative for vegetable and fruit intake, information about their actual effects on kidney function is sparse. The aim of this study was to determine the association between the consumption of vegetable and fruit juices and changes in kidney function in a Japanese population over a 5-y period. Methods: In this prospective study, we analyzed 2755 Japanese (742 men and 2013 women) individuals who participated in both the baseline and follow-up surveys in the Daiko study (a study within the Japan Multi-Institutional Collaborative Cohort study). Estimated glomerular filtration rate (eGFR) was calculated by age, sex, and serum creatinine level. For each beverage, we categorized all participants into four groups—rare (rarely consumed), low (≤2 cups/wk), moderate (3–4 cups/wk), or frequent (≥5 cups/wk) consumers of the beverage—based on a food frequency questionnaire. Results: The mean baseline and follow-up eGFR (SD) were 82.4 (14.6) and 72.2 (12.6), respectively. In fully adjusted regression analyses, moderate consumption of vegetable juice was associated a lower decline in eGFR compared with the rare consumption group (β = –1.30; P = 0.01). Moreover, stratified analyses revealed that this significant association remained in those who were young, female, non-obese, normotensive, smoked cigarettes, consumed alcohol, or exercised. However, no significant association was found in analyses for fruit juices. Conclusions: This 5-y prospective study suggested an association between self-reported moderate consumption of vegetable juice and changes (possibly smaller decline) in kidney function in a relatively healthy Japanese population.

DOI： 10.1016/j.nut.2020.111114

Body mass index and colorectal cancer risk: A Mendelian randomization study Reviewed International journal

Suzuki Shiori, Goto Atsushi, Nakatochi Masahiro, Narita Akira, Yamaji Taiki, Sawada Norie, Katagiri Ryoko, Iwagami Masao, Hanyuda Akiko, Hachiya Tsuyoshi, Sutoh Yoichi, Oze Isao, Koyanagi Yuriko N., Kasugai Yumiko, Taniyama Yukari, Ito Hidemi, Ikezaki Hiroaki, Nishida Yuichiro, Tamura Takashi, Mikami Haruo, Takezaki Toshiro, Suzuki Sadao, Ozaki Etsuko, Kuriki Kiyonori, Takashima Naoyuki, Arisawa Kokichi, Takeuchi Kenji, Tanno Kozo, Shimizu Atsushi, Tamiya Gen, Hozawa Atsushi, Kinoshita Kengo, Wakai Kenji, Sasaki Makoto, Yamamoto Masayuki, Matsuo Keitaro, Tsugane Shoichiro, Iwasaki Motoki

CANCER SCIENCE Vol. 112 ( 4 ) page： 1579 - 1588 2021.4

Language：English Publishing type：Research paper (scientific journal) Publisher：Cancer Science

Traditional observational studies have reported a positive association between higher body mass index (BMI) and the risk of colorectal cancer (CRC). However, evidence from other approaches to pursue the causal relationship between BMI and CRC is sparse. A two-sample Mendelian randomization (MR) study was undertaken using 68 single nucleotide polymorphisms (SNPs) from the Japanese genome-wide association study (GWAS) and 654 SNPs from the GWAS catalogue for BMI as sets of instrumental variables. For the analysis of SNP-BMI associations, we undertook a meta-analysis with 36 303 participants in the Japanese Consortium of Genetic Epidemiology studies (J-CGE), comprising normal populations. For the analysis of SNP-CRC associations, we utilized 7636 CRC cases and 37 141 controls from five studies in Japan, and undertook a meta-analysis. Mendelian randomization analysis of inverse-variance weighted method indicated that a one-unit (kg/m2) increase in genetically predicted BMI was associated with an odds ratio of 1.13 (95% confidence interval, 1.06-1.20; P value <.001) for CRC using the set of 68 SNPs, and an odds ratio of 1.07 (1.03-1.11, 0.001) for CRC using the set of 654 SNPs. Sensitivity analyses robustly showed increased odds ratios for CRC for every one-unit increase in genetically predicted BMI. Our MR analyses strongly support the evidence that higher BMI influences the risk of CRC. Although Asians are generally leaner than Europeans and North Americans, avoiding higher BMI seems to be important for the prevention of CRC in Asian populations.

DOI： 10.1111/cas.14824

A genome-wide association study on fish consumption in a Japanese population-the Japan Multi-Institutional Collaborative Cohort study Reviewed International journal

Suzuki Taro, Nakamura Yasuyuki, Matsuo Keitaro, Oze Isao, Doi Yukio, Narita Akira, Shimizu Atsushi, Imaeda Nahomi, Goto Chiho, Matsui Kenji, Nakatochi Masahiro, Miura Katsuyuki, Takashima Naoyuki, Kuriki Kiyonori, Shimanoe Chisato, Tanaka Keitaro, Ikezaki Hiroaki, Murata Masayuki, Ibusuki Rie, Takezaki Toshiro, Koyanagi Yuriko, Ito Hidemi, Matsui Daisuke, Koyama Teruhide, Mikami Haruo, Nakamura Yohko, Suzuki Sadao, Nishiyama Takeshi, Katsuura-Kamano Sakurako, Arisawa Kokichi, Takeuchi Kenji, Tamura Takashi, Okada Rieko, Kubo Yoko, Momozawa Yukihide, Kubo Michiaki, Kita Yoshikuni, Wakai Kenji, Nagase Hiroki, Narimatsu Hiroto, Uehara Ritei

EUROPEAN JOURNAL OF CLINICAL NUTRITION Vol. 75 ( 3 ) page： 480 - 488 2021.3

Language：English Publishing type：Research paper (scientific journal) Publisher：European Journal of Clinical Nutrition

Background/objective: Although benefits of fish consumption for health are well known, a significant percentage of individuals dislike eating fish. Fish consumption may be influenced by genetic factors in addition to environmental factors. We conducted a genome-wide association study (GWAS) to find genetic variations that affect fish consumption in a Japanese population. Methods: We performed a two-stage GWAS on fish consumption using 13,739 discovery samples from the Japan Multi-Institutional Collaborative Cohort study, and 2845 replication samples from the other population. We used a semi-quantitative food frequency questionnaire to estimate food intake. Association of the imputed variants with fish consumption was analyzed by separate linear regression models per variant, with adjustments for age, sex, energy intake, principal component analysis components 1–10, and alcohol intake (g/day). We also performed conditional analysis. Results: We found 27 single nucleotide polymorphisms (SNPs) located in 12q24 and 14q32.12 that were associated with fish consumption. The 19 SNPs were located at 11 genes including six lead SNPs at the BRAP, ACAD10, ALDH2, NAA25, and HECTD4 regions on 12q24.12-13, and CCDC197 region on 14q32.12. In replication samples, all five SNPs located on chromosome 12 were replicated successfully, but the one on chromosome 14 was not. Conditional analyses revealed that the five lead variants in chromosome 12 were in fact the same signal. Conclusion: We found that new SNPs in the 12q24 locus were related to fish intake in two Japanese populations. The associations between SNPs on chromosome 12 and fish intake were strongly confounded by drinking status.

DOI： 10.1038/s41430-020-00702-7

Both variants of A1CF and BAZ1B genes are associated with gout susceptibility: a replication study and meta-analysis in a Japanese population Reviewed International journal

Kawaguchi Makoto, Nakayama Akiyoshi, Aoyagi Yuka, Nakamura Takahiro, Shimizu Seiko, Kawamura Yusuke, Takao Mikiya, Tamura Takashi, Hishida Asahi, Nagayoshi Mako, Nagase Mitsuo, Ooyama Keiko, Ooyama Hiroshi, Shinomiya Nariyoshi, Matsuo Hirotaka

HUMAN CELL Vol. 34 ( 2 ) page： 293 - 299 2021.3

Language：English Publishing type：Research paper (scientific journal) Publisher：Human Cell

Gout is a common type of acute arthritis that results from elevated serum uric acid (SUA) levels. Recent genome-wide association studies (GWASs) have revealed several novel single nucleotide polymorphism (SNPs) associated with SUA levels. Of these, rs10821905 of A1CF and rs1178977 of BAZ1B showed the greatest and the second greatest significant effect size for increasing SUA level in the Japanese population, but their association with gout is not clear. We examined their association with gout using 1411 clinically-defined Japanese gout patients and 1285 controls, and meta-analyzed our previous gout GWAS data to investigate any association with gout. Replication studies revealed both SNPs to be significantly associated with gout (P = 0.0366, odds ratio [OR] with 95% confidence interval [CI]: 1.30 [1.02–1.68] for rs10821905 of A1CF, P = 6.49 × 10–3, OR with 95% CI: 1.29 [1.07–1.55] for rs1178977 of BAZ1B). Meta-analysis also revealed a significant association with gout in both SNPs (Pmeta = 3.16 × 10–4, OR with 95% CI: 1.39 [1.17–1.66] for rs10821905 of A1CF, Pmeta = 7.28 × 10–5, OR with 95% CI 1.32 [1.15–1.51] for rs1178977 of BAZ1B). This study shows the first known association between SNPs of A1CF, BAZ1B and clinically-defined gout cases in Japanese. Our results also suggest a shared physiological/pathophysiological background between several populations, including Japanese, for both SUA increase and gout susceptibility. Our findings will not only assist the elucidation of the pathophysiology of gout and hyperuricemia, but also suggest new molecular targets.

DOI： 10.1007/s13577-021-00485-4

Assessing the relationship between high-sensitivity C-reactive protein and kidney function employing mendelian randomization in a Japanese community based J-MICC Study. Reviewed

Fujii R, Hishida A, Nishiyama T, Nakatochi M, Matsuo K, Ito H, Nishida Y, Shimanoe C, Nakamura Y, Turin TC, Suzuki S, Watanabe M, Ibusuki R, Takezaki T, Mikami H, Nakamura Y, Ikezaki H, Murata M, Kuriki K, Kuriyama N, Matsui D, Arisawa K, Katsuura-Kamano S, Tsukamoto M, Tamura T, Kubo Y, Kondo T, Momozawa Y, Kubo M, Takeuchi K, Wakai K

Journal of epidemiology 2021.2

Language：English Publishing type：Research paper (scientific journal) Publisher：日本疫学会

Background: Inflammation is thought to be a risk factor for kidney disease. However, whether inflammatory status is either a cause or an outcome of chronic kidney disease remains controversial. We aimed to investigate the causal relationship between high-sensitivity C-reactive protein (hs-CRP) and estimated glomerular filtration rate (eGFR) using Mendelian randomization (MR) approaches.Methods: A total of 10,521 participants of the Japan Multi-institutional Collaborative Cohort Study was analyzed in this study. We used two-sample MR approaches (the inverse-variance weighted (IVW), the weighted median (WM), and the MR-Egger method) to estimate the effect of genetically determined hs-CRP on kidney function. We selected four and three hs-CRP associated single nucleotide polymorphisms (SNPs) as two instrumental variables (IV): IVCRP and IVAsian, based on SNPs previously identified in European and Asian populations. IVCRP and IVAsian explained 3.4% and 3.9% of the variation in hs-CRP, respectively.Results: Using the IVCRP, genetically determined hs-CRP was not significantly associated with eGFR in the IVW and the WM methods (estimate per 1 unit increase in ln(hs-CRP), 0.000; 95% confidence interval [CI], −0.019 to 0.020 and −0.003; 95% CI, −0.019 to 0.014, respectively). For IVAsian, we found similar results using the IVW and the WM methods (estimate, 0.005; 95% CI, −0.020 to 0.010 and −0.004; 95% CI, −0.020 to 0.012, respectively). The MR-Egger method also showed no causal relationships between hs-CRP and eGFR (IVCRP: −0.008; 95% CI, −0.058 to 0.042; IVAsian: 0.001; 95% CI, −0.036 to 0.036).Conclusions: Our two-sample MR analyses with different IVs did not support a causal effect of hs-CRP on eGFR.

DOI： 10.2188/jea.JE20200540

Genome-wide association study of serum prostate-specific antigen levels based on 1000 Genomes imputed data in Japanese: the Japan Multi-Institutional Collaborative Cohort Study Reviewed

Hishida Asahi, Nakatochi Masahiro, Tamura Takashi, Nagayoshi Mako, Okada Rieko, Kubo Yoko, Tsukamoto Mineko, Kadomatsu Yuka, Suzuki Sadao, Nishiyama Takeshi, Kuriyama Nagato, Watanabe Isao, Takezaki Toshiro, Nishimoto Daisaku, Kuriki Kiyonori, Arisawa Kokichi, Katsuura-Kamano Sakurako, Mikami Haruo, Kusakabe Miho, Oze Isao, Koyanagi Yuriko N., Nakamura Yasuyuki, Kadota Aya, Shimanoe Chisato, Tanaka Keitaro, Ikezaki Hiroaki, Murata Masayuki, Kubo Michiaki, Momozawa Yukihide, Takeuchi Kenji, Wakai Kenji

NAGOYA JOURNAL OF MEDICAL SCIENCE Vol. 83 ( 1 ) page： 183 - 194 2021.2

Language：English Publishing type：Research paper (scientific journal) Publisher：Nagoya Journal of Medical Science

Prostate cancer is emerging as a significant global public health burden. The incidence and prevalence of prostate cancer has increased in Japan, as westernized lifestyles become more popular. Recent advances in genetic epidemiology, including genome-wide association studies (GWASs), have identified considerable numbers of human genetic factors associated with diseases. Several GWASs have reported significant loci associated with serum prostate-specific antigen (PSA) levels. One GWAS, which was based on classic GWAS microarray measurements, has been reported for Japanese so far. In the present study,we conducted a GWAS of serum PSA using 1000Genomes imputed GWAS data (n =1,216) from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study, to detect candidate novel genetic loci that influence serum PSA levels in Japanese. The association of SNPs/genetic variants with serum PSA as a continuous variable was tested using the linear Wald test. SNP rs10000006 in SGMS2 (sphingomyelin synthase 2) on chromosome 4 had genome-wide significance (P <5×10∑8), and eight variants on three chromosomes (chromosomes 12, 14, 15) had genome-wide suggestive levels of significance (P <1×10∑6). With an independent data set from the J-MICC Shizuoka Study (n = 2,447), the association of the SGMS2 SNP with blood PSA levels was not replicated. Although our GWAS failed to detect novel loci associated with serum PSA levels in the Japanese cohort, it confirmed the significant effects of previously reported genetic loci on PSA levels in Japanese. Importantly, our results confirmed the significance of KLK3 SNPs also in Japanese, implying that consideration of individual genetic information in prostate cancer diagnosis may be possible in the future.

DOI： 10.18999/nagjms.83.1.183

Impact of PSCA polymorphisms on the risk of duodenal ulcer. Reviewed

Yoshiaki Usui, Keitaro Matsuo, Isao Oze, Tomotaka Ugai, Yuriko Koyanagi, Yoshinobu Maeda, Hidemi Ito, Asahi Hishida, Kenji Takeuchi, Takashi Tamura, Mineko Tsukamoto, Yuka Kadomatsu, Megumi Hara, Yuichiro Nishida, Ippei Shimoshikiryo, Toshiro Takezaki, Etsuko Ozaki, Daisuke Matsui, Isao Watanabe, Sadao Suzuki, Miki Watanabe, Hiroko Nakagawa-Senda, Haruo Mikami, Yohko Nakamura, Kokichi Arisawa, Hirokazu Uemura, Kiyonori Kuriki, Naoyuki Takashima, Aya Kadota, Hiroaki Ikezaki, Masayuki Murata, Masahiro Nakatochi, Yukihide Momozawa, Michiaki Kubo, Kenji Wakai

Journal of epidemiology Vol. 31 ( 1 ) page： 12 - 20 2021.1

Language：English Publishing type：Research paper (scientific journal) Publisher：Japan Epidemiological Association

BACKGROUND: While duodenal ulcer (DU) and gastric cancer (GC) are both H. pylori infection-related diseases, individuals with DU are known to have lower risk for GC. Many epidemiological studies have identified the PSCA rs2294008 T-allele as a risk factor of GC, while others have found an association between the rs2294008 C-allele and risk of DU and gastric ulcer (GU). Following these initial reports, however, few studies have since validated these associations. Here, we aimed to validate the association between variations in PSCA and the risk of DU/GU and evaluate its interaction with environmental factors in a Japanese population. METHODS: PSCA six SNPs were genotyped in 584 DU cases, 925 GU cases, and 8,105 controls from the Japan Multi-Institutional Collaborative Cohort (J-MICC). Unconditional logistic regression models were applied to estimate odds ratios (ORs) and 95% confidence intervals (CI) for association between the SNPs and risk of DU/GU. RESULTS: PSCA rs2294008 C-allele was associated with per allele OR of 1.34 (95% CI, 1.18-1.51; P=2.28×10-6) for the risk of DU. This association was independent of age, sex, study site, smoking habit, drinking habit and H. pylori status. On the other hand, we did not observe an association between the risk of GU and PSCA SNPs. CONCLUSIONS: Our study confirms an association between the PSCA rs2294008 C-allele and the risk of DU in a Japanese population.

DOI： 10.2188/jea.JE20190184

Associations between peroxisome proliferator-activated receptor gamma (PPAR-gamma ) polymorphisms and serum lipids: Two cross-sectional studies of community-dwelling adults Reviewed International journal

Matsunaga Takashi, Naito Mariko, Yin Guang, Hishida Asahi, Okada Rieko, Kawai Sayo, Sasakabe Tae, Kadomatsu Yuka, Tsukamoto Mineko, Kubo Yoko, Tamura Takashi, Takeuchi Kenji, Mori Atsuyoshi, Hamajima Nobuyuki, Wakai Kenji

GENE Vol. 762 page： 145019 2020.12

Language：English Publishing type：Research paper (scientific journal) Publisher：Gene

Dyslipidemia is a well-established risk factor for cardiovascular disease. Experimental studies have reported that peroxisome proliferator-activated receptor γ (PPAR-γ) regulates adipocyte differentiation, lipid storage, and glucose metabolism. Therefore, we examined the associations between PPAR-γ polymorphisms (rs1801282, rs3856806, rs12497191, rs1151999, and rs1152003) and serum lipids in two cross-sectional studies. In the Shizuoka area of the Japan Multi-Institutional Collaborative Cohort Study, we examined 4,952 participants (3,356 men and 1,596 women) in a baseline survey and 2,245 participants (1,550 men and 695 women) in a second survey 5 years later. Outcome measures were the prevalence of dyslipidemia (low-density lipoprotein-cholesterol [LDL-C] ≥ 140 mg/dl, high-density lipoprotein-cholesterol < 40 mg/dl, triglycerides ≥ 150 mg/dl, and/or use of cholesterol-lowering drugs) and the prevalence of high LDL-C (LDL-C ≥ 140 mg/dl and/or use of cholesterol-lowering drugs). Multivariate odds ratios (ORs) were estimated by using unconditional logistic regression models. A total of 2,114 and 1,431 individuals (42.7% and 28.9%) had dyslipidemia and high LDL-C in the baseline survey, respectively, as did 933 and 716 (41.6% and 31.9%), respectively, in the second survey. In the baseline study, compared with major allele homozygotes, minor allele homozygotes of rs3856806 and rs12497191 had a 42% (OR, 0.58; 95% confidence interval (CI), 0.39–0.85) and 23% (OR, 0.77; 95% CI, 0.60–0.99) lower risk of dyslipidemia, respectively, after adjustment for potential confounding factors. In addition, minor allele homozygotes of rs3856806 had a 45% (OR, 0.55; 95% CI, 0.35–0.86) lower risk of high LDL-C. Similar risk reductions were found in the second survey. In conclusion, rs3856806 and rs12497191 polymorphisms may be related to a lower risk of dyslipidemia and high LDL-C.

DOI： 10.1016/j.gene.2020.145019

Association between alcohol intake pattern and metabolic syndrome components and simulated change by alcohol intake reduction: A cross-sectional study from the Japan Multi-Institutional Collaborative Cohort Study Reviewed International journal

Shimoshikiryo Ippei, Ibusuki Rie, Shimatani Keiichi, Nishimoto Daisaku, Takezaki Toshiro, Nishida Yuichiro, Shimanoe Chisato, Hishida Asahi, Tamura Takashi, Okada Rieko, Kubo Yoko, Ozaki Etsuko, Matsui Daisuke, Suzuki Sadao, Nakagawa-Senda Hiroko, Kuriki Kiyonori, Kita Yoshikuni, Takashima Naoyuki, Arisawa Kokichi, Uemura Hirokazu, Ikezaki Hiroaki, Furusyo Norihiro, Oze Isao, Koyanagi Yuriko N., Mikami Haruo, Nakamura Yohko, Naito Mariko, Wakai Kenji

ALCOHOL Vol. 89 page： 129 - 138 2020.12

Language：English Publishing type：Research paper (scientific journal) Publisher：Alcohol

To investigate the association between alcohol intake pattern in amount and frequency and metabolic syndrome (Mets) components, we simulated the change in the prevalence of Mets components by intake reduction. In order to manage Mets, alcohol intake reduction with moderation of intake pattern is required. However, evidence investigating the comparative impact of alcohol intake reduction in amount and frequency for Mets components is limited. We conducted a large-scale cross-sectional study in the general Japanese population. The study subjects included 37,371 non-drinkers and current drinkers recruited in the Japan Multi-Institutional Collaborative Cohort Study. Odds ratios (ORs) for Mets components according to alcohol intake amount and frequency were estimated using a multiple logistic regression model. The prevalence of Mets components was estimated after assumed alcohol intake reduction of a) none, b) 10 g/day (men) or 5 g/day (women), c) 20 g/day (men) or 10 g/day (women), d) less than 20 g/day (men) or 10 g/day (women) for moderate-to-heavy drinkers, e) 1–2 times/week, and f) 3–4 times/week. The ORs with alcohol intake amount and frequency increased with high blood pressure while decreasing with dyslipidemia. A J-shaped association was observed between intake amount and Mets. The estimated prevalence (%) of high blood pressure and dyslipidemia in men were a) 45.2, b) 43.0, c) 41.4, d) 40.4, e) 42.9, and f) 42.0; and a) 50.3, b) 51.8, c) 52.9, d) 50.2, e) 52.7, and f) 53.4 in women. The estimated prevalence of high blood pressure in women did not evidently decrease. Simulated alcohol intake reduction showed decreased prevalence for high blood pressure and increased prevalence for dyslipidemia in men after reduced intake amount and frequency. The largest decreased prevalence for high blood pressure was observed in men when all moderate-to-heavy drinkers reduced their alcohol intake amount to less than 20 g/day.

DOI： 10.1016/j.alcohol.2020.09.002

Association between plasma levels of homocysteine, folate, and vitamin B-12, and dietary folate intake and hypertension in a cross-sectional study Reviewed International journal

Tamura Takashi, Kuriyama Nagato, Koyama Teruhide, Ozaki Etsuko, Matsui Daisuke, Kadomatsu Yuka, Tsukamoto Mineko, Kubo Yoko, Okada Rieko, Hishida Asahi, Sasakabe Tae, Kawai Sayo, Naito Mariko, Takashima Naoyuki, Kadota Aya, Tanaka Keitaro, Hara Megumi, Suzuki Sadao, Nakagawa-Senda Hiroko, Takezaki Toshiro, Shimoshikiryo Ippei, Ikezaki Hiroaki, Murata Masayuki, Oze Isao, Ito Hidemi, Mikami Haruo, Nakamura Yohko, Kuriki Kiyonori, Arisawa Kokichi, Uemura Hirokazu, Takeuchi Kenji, Wakai Kenji

SCIENTIFIC REPORTS Vol. 10 ( 1 ) page： 18499 2020.10

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Scientific Reports

There are few studies examining the association between homocysteine (Hcy) level and the risk of hypertension with consideration for folate and vitamin B12 as related to Hcy level. We simultaneously examined the associations of plasma levels of Hcy, folate, and vitamin B12, and dietary folate intake with the prevalence of hypertension. Participants included 1046 men and 1033 women (mean age ± standard deviation: 56.0 ± 8.9 years) in the Japan Multi-Institutional Collaborative Cohort Study. Dietary folate intake was estimated using a validated food frequency questionnaire. Hypertension was defined based on measured blood pressure and use of antihypertensive medication. A total of 734 participants (35.3%) had hypertension. Multivariate-adjusted odds ratios of hypertension for the highest quartile group of Hcy were 2.36 (95% CI 1.41–3.96) in men and 1.86 (95% CI 1.11–3.11) in women, as compared with the lowest group (P for trend = 0.014 and 0.005, respectively). Dietary folate intake was not correlated with hypertension in both men and women (P for trend = 0.099 and 0.703, respectively). Plasma vitamin B12 was positively associated with hypertension only in women (P for trend = 0.027). Plasma Hcy level was positively linked with hypertension after controlling for covariates, including folate and vitamin B12.

DOI： 10.1038/s41598-020-75267-3

Study profile of the Japan Multi-institutional Collaborative Cohort (J-MICC) Study. Reviewed

Takeuchi K, Naito M, Kawai S, Tsukamoto M, Kadomatsu Y, Kubo Y, Okada R, Nagayoshi M, Tamura T, Hishida A, Nakatochi M, Sasakabe T, Hashimoto S, Eguchi H, Momozawa Y, Ikezaki H, Murata M, Furusyo N, Tanaka K, Hara M, Nishida Y, Matsuo K, Ito H, Oze I, Mikami H, Nakamura Y, Kusakabe M, Takezaki T, Ibusuki R, Shimoshikiryo I, Suzuki S, Nishiyama T, Watanabe M, Koyama T, Ozaki E, Watanabe I, Kuriki K, Kita Y, Ueshima H, Matsui K, Arisawa K, Uemura H, Katsuura-Kamano S, Nakamura S, Narimatsu H, Hamajima N, Tanaka H, Wakai K

Journal of epidemiology 2020.9

Language：English Publishing type：Research paper (scientific journal) Publisher：日本疫学会

Background: The Japan Multi-institutional Collaborative Cohort (J-MICC) study was launched in 2005 to examine gene–environment interactions in lifestyle-related diseases, including cancers, among the Japanese. This report describes the study design and baseline profile of the study participants.Methods: The participants of the J-MICC Study were individuals aged 35 to 69 years enrolled from respondents to study announcements in specified regions, inhabitants attending health checkup examinations provided by local governments, visitors at health checkup centers, and first-visit patients at a cancer hospital in Japan. At the time of the baseline survey, from 2005 to 2014, we obtained comprehensive information regarding demographics, education, alcohol consumption, smoking, sleeping, exercise, food intake frequency, medication and supplement use, personal and family disease history, psychological stress, and female reproductive history and collected peripheral blood samples.Results: The baseline survey included 92,610 adults (mean age: 55.2 [standard deviation, 9.4] years, 44.1% men) from 14 study regions in 12 prefectures. The participation rate was 33.5%, with participation ranging from 19.7% to 69.8% in different study regions. The largest number of participants was in the age groups of 65–69 years for men and 60–64 years for women. There were differences in body mass index, educational attainment, alcohol consumption, smoking, and sleep duration between men and women.Conclusions: The J-MICC Study collected lifestyle and clinical data and biospecimens from over 90,000 participants. This cohort is expected to be a valuable resource for the national and international scientific community in providing evidence to support longer healthy lives.

DOI： 10.2188/jea.JE20200147

Association of Dietary Acid Load with the Prevalence of Metabolic Syndrome among Participants in Baseline Survey of the Japan Multi-Institutional Collaborative Cohort Study. Reviewed International journal

Kokichi Arisawa, Sakurako Katsuura-Kamano, Hirokazu Uemura, Nguyen Van Tien, Asahi Hishida, Takashi Tamura, Yoko Kubo, Mineko Tsukamoto, Keitaro Tanaka, Megumi Hara, Toshiro Takezaki, Daisaku Nishimoto, Teruhide Koyama, Etsuko Ozaki, Sadao Suzuki, Takeshi Nishiyama, Kiyonori Kuriki, Aya Kadota, Naoyuki Takashima, Hiroaki Ikezaki, Masayuki Murata, Isao Oze, Keitaro Matsuo, Haruo Mikami, Yohko Nakamura, Kenji Takeuchi, Kenji Wakai

Nutrients Vol. 12 ( 6 ) 2020.6

Language：English Publishing type：Research paper (scientific journal)

The association between dietary acid load and metabolic syndrome (MetS) has not been fully investigated. A cross-sectional study was performed on 14,042 men and 14,105 women (aged 35-69 years) who participated in a baseline survey of the Japan Multi-Institutional Collaborative Cohort study. Dietary acid load was assessed using the net-endogenous-acid-production (NEAP) score that is closely correlated with the rate of renal net acid excretion. MetS was diagnosed according to the Joint Interim Statement Criteria of 2009 using body-mass index instead of waist circumference. After adjusting for potential confounders, higher NEAP scores were associated with a significantly increased odds ratio (OR) of MetS, obesity, high blood pressure, and high fasting blood glucose. These associations remained significant after further adjustment for carbohydrate intake or two nutrient-pattern scores significantly associated with MetS. After adjustment for fiber, iron, potassium, and vitamin pattern scores, the OR of MetS for the highest quartile of NEAP scores, relative to the lowest quartile, was 1.25 (95% confidence interval 1.12-1.39). There was no significant interaction between sex, age, or body-mass index and NEAP. Higher dietary acid load was associated with a higher prevalence of MetS and several of its components, independently of carbohydrate intake or nutrient patterns.

DOI： 10.3390/nu12061605

Associations between Exposure to Tobacco Smoke and Behavioral Problems in Preschool Japanese Children Reviewed International journal

Wada, K; Ueyama, J; Konishi, K; Goto, Y; Koda, S; Mizuta, F; Tamura, T; Watanabe, K; Ando, K; Kondo, T; Nagata, C

JOURNAL OF ENVIRONMENTAL AND PUBLIC HEALTH Vol. 2020 page： 7591263 2020.5

Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Environmental and Public Health

Background. A few studies related to pediatric behavior have measured secondhand smoke exposure in children using valid objective biochemical markers. We aimed at investigating the associations between current and cumulative exposure to tobacco smoke, measured both subjectively and objectively, and behavioral problems in children. Methods. Subjects were 437 Japanese children, aged 3-6 years in 2006. Exposure to tobacco smoke was evaluated from a parent-administered questionnaire and urinary cotinine concentrations. The cotinine concentrations were measured using first-void morning urine by liquid chromatography-tandem mass spectrometry. Children's behaviors were assessed by the parent-completed Strengths and Difficulties Questionnaire. Results. After multiple adjustments for covariates, higher total difficulty scores of children were significantly associated with the larger number of cigarettes parents smoke, more smokers among cohabiters, and more pack-years of exposure to tobacco smoke from parents and cohabiters. The total difficulty scores were 8.72, 9.09, and 10.52, respectively, for children in the low, middle, and high tertiles of creatinine-corrected cotinine concentrations in urine (p=0.002, trend p=0.005). There was no substantial sex difference in the positive associations between passive smoking and the SDQ scores. Conclusions. Exposure to tobacco smoke in early childhood may be involved in the development of pediatric behavioral problems. The importance of reducing the exposure of children to tobacco smoke, particularly in the home, was further emphasized for the prevention of psychological and behavioral problems in childhood.

DOI： 10.1155/2020/7591263

Subtype-specific gout susceptibility loci and enrichment of selection pressure on ABCG2 and ALDH2 identified by subtype genome-wide meta-analyses of clinically defined gout patients Reviewed International journal

Nakayama Akiyoshi, Nakatochi Masahiro, Kawamura Yusuke, Yamamoto Ken, Nakaoka Hirofumi, Shimizu Seiko, Higashino Toshihide, Koyama Teruhide, Hishida Asahi, Kuriki Kiyonori, Watanabe Miki, Shimizu Toru, Ooyama Keiko, Ooyama Hiroshi, Nagase Mitsuo, Hidaka Yuji, Matsui Daisuke, Tamura Takashi, Nishiyama Takeshi, Shimanoe Chisato, Katsuura-Kamano Sakurako, Takashima Naoyuki, Shirai Yuya, Kawaguchi Makoto, Takao Mikiya, Sugiyama Ryo, Takada Yuzo, Nakamura Takahiro, Nakashima Hiroshi, Tsunoda Masashi, Danjoh Inaho, Hozawa Atsushi, Hosomichi Kazuyoshi, Toyoda Yu, Kubota Yu, Takada Tappei, Suzuki Hiroshi, Stiburkova Blanka, Major Tanya J., Merriman Tony R., Kuriyama Nagato, Mikami Haruo, Takezaki Toshiro, Matsuo Keitaro, Suzuki Sadao, Hosoya Tatsuo, Kamatani Yoichiro, Kubo Michiaki, Ichida Kimiyoshi, Wakai Kenji, Inoue Ituro, Okada Yukinori, Shinomiya Nariyoshi, Matsuo Hirotaka

ANNALS OF THE RHEUMATIC DISEASES Vol. 79 ( 5 ) page： 657 - 665 2020.5

Language：English Publishing type：Research paper (scientific journal) Publisher：Annals of the Rheumatic Diseases

Objectives Genome-wide meta-analyses of clinically defined gout were performed to identify subtype-specific susceptibility loci. Evaluation using selection pressure analysis with these loci was also conducted to investigate genetic risks characteristic of the Japanese population over the last 2000-3000 years. Methods Two genome-wide association studies (GWASs) of 3053 clinically defined gout cases and 4554 controls from Japanese males were performed using the Japonica Array and Illumina Array platforms. About 7.2 million single-nucleotide polymorphisms were meta-analysed after imputation. Patients were then divided into four clinical subtypes (the renal underexcretion type, renal overload type, combined type and normal type), and meta-analyses were conducted in the same manner. Selection pressure analyses using singleton density score were also performed on each subtype. Results In addition to the eight loci we reported previously, two novel loci, PIBF1 and ACSM2B, were identified at a genome-wide significance level (p<5.0×10-8) from a GWAS meta-analysis of all gout patients, and other two novel intergenic loci, CD2-PTGFRN and SLC28A3-NTRK2, from normal type gout patients. Subtype-dependent patterns of Manhattan plots were observed with subtype GWASs of gout patients, indicating that these subtype-specific loci suggest differences in pathophysiology along patients' gout subtypes. Selection pressure analysis revealed significant enrichment of selection pressure on ABCG2 in addition to ALDH2 loci for all subtypes except for normal type gout. Conclusions Our findings on subtype GWAS meta-analyses and selection pressure analysis of gout will assist elucidation of the subtype-dependent molecular targets and evolutionary involvement among genotype, phenotype and subtype-specific tailor-made medicine/prevention of gout and hyperuricaemia.

DOI： 10.1136/annrheumdis-2019-216644

Combined effect of weight gain within normal weight range and parental hypertension on the prevalence of hypertension; from the J-MICC Study Reviewed International journal

Okada Rieko, Kadomatsu Yuka, Tsukamoto Mineko, Sasakabe Tae, Kawai Sayo, Tamura Takashi, Hishida Asahi, Ikezaki Hiroaki, Furusyo Norihiro, Tanaka Keitaro, Hara Megumi, Suzuki Sadao, Watanabe Miki, Takezaki Toshiro, Nishimoto Daisaku, Matsui Daisuke, Watanabe Isao, Kuriki Kiyonori, Takashima Naoyuki, Nakamura Yoshimasa, Katsuura-Kamano Sakurako, Arisawa Kokichi, Mikami Haruo, Nakamura Yoko, Oze Isao, Koyanagi Yuriko N., Naito Mariko Fujimoto, Wakai Kenji

JOURNAL OF HUMAN HYPERTENSION Vol. 34 ( 2 ) page： 125 - 131 2020.2

Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Human Hypertension

The aim of this study is to show the combined effect of weight gain within normal weight range in adulthood and parental HT on the prevalence of HT. The study subjects were 44,998 individuals (19,039 men and 25,959 women) with normal weight (body mass index [BMI] 18.5–24.9) aged 35–69 years who participated in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. They were categorized into six groups by weight gain from age 20 years (<10 kg, and ≥10 kg) and by the number of parents having HT (no parent, one parent, and both parents). Odds ratios for HT were estimated after adjustment for age, sex, current BMI, estimated daily sodium intake, and other confounding factors. The prevalence of HT (31.5% in total subjects) gradually increased with greater weight gain from age 20 years and with greater number of parents with HT. Subjects who gained weight ≥10 kg and having both parents with HT showed the highest risk of having HT compared with those who gained weight <10 kg without parental HT (59.8% vs. 24.9%, odds ratio 4.25, 95% CI 3.53–5.13 after adjustment). This association was similarly observed in any category of age, sex, and BMI. Subjects who gained weight within normal range of BMI and having one or both parent(s) with HT showed the higher risk of having HT independent of their attained BMI in their middle ages. Thus, subjects having parent(s) with HT should avoid gaining their weight during adulthood, even within normal range of BMI, to reduce the risk of having HT.

DOI： 10.1038/s41371-019-0230-y

Associations between diet and mental health using the 12-item General Health Questionnaire: cross-sectional and prospective analyses from the Japan Multi-Institutional Collaborative Cohort Study. Reviewed International journal

Naoki Choda, Kenji Wakai, Mariko Naito, Nahomi Imaeda, Chiho Goto, Kenta Maruyama, Yuka Kadomatsu, Mineko Tsukamoto, Tae Sasakabe, Yoko Kubo, Rieko Okada, Sayo Kawai, Takashi Tamura, Asahi Hishida, Kenji Takeuchi, Atsuyoshi Mori, Nobuyuki Hamajima

Nutrition journal Vol. 19 ( 1 ) page： 2 - 2 2020.1

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Mental health has become a major public health issue worldwide. Biological and epidemiological studies suggest diet has a role in the prevention or cure of mental disorders. However, further research is required to elucidate the relationship between diet and mental health. This study aimed to investigate associations between dietary intake of nutrients (macronutrients, vitamins, calcium, and fatty acids) and food groups (fish, meat and chicken, dairy products, and vegetables) and mental health among middle-aged Japanese in cross-sectional and prospective studies. METHODS: In total, 9298 men and women that participated in two areas of the Japan Multi-Institutional Collaborative Cohort Study were eligible for analysis at the baseline (cross-sectional) survey. Of these, 4701 participants were followed for about 5 years and included in the follow-up (prospective) analysis. The 12-item General Health Questionnaire (GHQ) was used to assess participants' general mental health status over the past several weeks. The average intake of 46 foods over the past year was assessed by a validated food frequency questionnaire. We also evaluated lifestyle and medical factors using a self-administered questionnaire. A cross-sectional logistic regression analysis was performed to estimate odds ratios for a GHQ score ≥ 4 (poor mental health) according to dietary intake of foods/nutrients at baseline. The prospective study used baseline dietary and lifestyle factors and GHQ scores at follow-up. RESULTS: The cross-sectional logistic regression analysis showed vegetables, protein, calcium, vitamin D, carotene and n-3 highly-polyunsaturated fatty acids were inversely associated with a GHQ score ≥ 4. On the other hand, mono-unsaturated fatty acids showed a positive association with higher GHQ score. The prospective logistic regression analysis found dairy products, calcium, vitamin B2, and saturated fatty acids were inversely correlated with a GHQ score ≥ 4. Calcium was associated with GHQ scores in both the cross-sectional and follow-up studies. In the follow-up study, the multivariable-adjusted odds ratio for a GHQ score ≥ 4 was 0.71 (95% confidence interval, 0.55-0.92) for the highest versus lowest quartiles of calorie-adjusted dietary calcium intake. CONCLUSION: Consuming particular nutrients and foods, especially calcium and dairy products, may lead to better mental health in Japanese adults.

DOI： 10.1186/s12937-019-0515-6

Dysfunctional missense variant of OAT10/ SLC22A13 decreases gout risk and serum uric acid levels Reviewed International journal

Higashino T, Morimoto K, Nakaoka H, Toyoda Y, Kawamura Y, Shimizu S, Nakamura T, Hosomichi K, Nakayama A, Ooyama K, Ooyama H, Shimizu T, Ueno M, Ito T, Tamura T, Naito M, Nakashima H, Kawaguchi M, Takao M, Kawai Y, Osada N, Ichida K, Yamamoto K, Suzuki H, Shinomiya N, Inoue I, Takada T, Matsuo H

Ann Rheum Dis Vol. 79 ( 1 ) page： 164 - 166 2020.1

Sedentary Time is Associated with Cardiometabolic Diseases in A Large Japanese Population: A Cross-Sectional Study Reviewed International journal

Koyama Teruhide, Kuriyama Nagato, Ozaki Etsuko, Tomida Satomi, Uehara Ritei, Nishida Yuichiro, Shimanoe Chisato, Hishida Asahi, Tamura Takashi, Tsukamoto Mineko, Kadomatsu Yuka, Oze Isao, Matsuo Keitaro, Mikami Haruo, Nakamura Yohko, Ibusuki Rie, Takezaki Toshiro, Suzuki Sadao, Nishiyama Takeshi, Kuriki Kiyonori, Takashima Naoyuki, Kadota Aya, Uemura Hirokazu, Katsuura-Kamano Sakurako, Ikezaki Hiroaki, Murata Masayuki, Takeuchi Kenji, Wakai Kenji

JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS Vol. 27 ( 10 ) page： 1097 - 1107 2020

Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Atherosclerosis and Thrombosis

Aim: Accumulating evidence reveals that sedentary behavior is associated with mortality and cardiometabolic disease; however, there are potential age and sex differences in sedentary behavior and health outcomes that have not been adequately addressed. This study aimed to determine the association of sedentary behavior with cardiometabolic diseases such as hypertension, dyslipidemia, diabetes mellitus, and its risk factors in a large Japanese population according to age and sex. Methods: Using data from the Japan Multi-Institutional Collaborative Cohort Study obtained from baseline surveys, data of 62,754 participants (27,930 males, 34,824 females) were analyzed. This study uses a cross-sectional design and self-administered questionnaires to evaluate sedentary time and anamnesis. For the logistic regression analysis, sedentary time ＜5 h/day was used as the reference and then adjusted for age, research areas, leisure-time metabolic equivalents, and alcohol and smoking status. From the analysis of anthropometric and blood examinations, 35,973 participants (17,109 males, 18,864 females) were analyzed. Results: For hypertension and diabetes, sedentary time was associated with a significantly higher proportion of male participants. Both sexes were associated with a significantly higher proportion of participants with dyslipidemia. Participants who had longer sedentary time tended to have increased levels of blood pressure, triglycerides, and non-high-density lipoprotein cholesterol (HDL-C), and decreased levels of HDL-C, especially in the 60–69 years group. Conclusions: Independent of leisure-time physical activity, sedentary time was associated with cardiometabolic diseases in a large Japanese population classified by age and sex. Our findings indicate that regularly interrupting and replacing sedentary time may contribute to better physical health-related quality of life.

DOI： 10.5551/jat.54320

Associations of Cell Phone Use and Screen Viewing with Overweight in Children Reviewed International journal

Wada Keiko, Yamakawa Michiyo, Konishi Kie, Goto Yuko, Mizuta Fumi, Koda Sachi, Uji Takahiro, Tamura Takashi, Nakamura Kozue, Tsuji Michiko, Nagai Hideshi, Itakura Naoko, Harada Kou, Takahara Osamu, Yamanaka Hiromichi, Nagata Chisato

CHILDHOOD OBESITY Vol. 15 ( 7 ) page： 417 - 425 2019.10

Language：English Publishing type：Research paper (scientific journal) Publisher：Childhood Obesity

Background: Effects of using mobile devices on childhood obesity have not been well studied. We aimed to ascertain whether cell phone use and screen viewing are associated with excess body weight in a cross-sectional study of Japanese school children. Methods: Subjects were 3141 students, ages 6 to 7 years, who participated in the Hekinan Children's Study conducted during 2011-2015. Participants were asked to submit a parent-administered questionnaire on child and parent demographics, health status, and lifestyles, including cell phone use and screen time. Heights and weights were measured at the schools. Being overweight was defined according to the cutoff point for children specified by the Extended International Obesity Task Force. Among 2596 analytic children, the odds ratios (ORs) for being overweight were estimated according to cell phone use, time spent watching television, and time spent on games and computers using the logistic regression models. Analyses were conducted after adjustments for potential confounders, including dietary intake, physical activities, sleep duration, and quality of sleep. Results: After multivariate adjustments, cell phone users were found to have an OR of 1.74 for being overweight compared with nonusers. Cell phone use of longer duration was associated with higher risk of being overweight (trend p = 0.018). Time spent watching television was positively associated with the risk of being overweight (trend p = 0.003). Conclusions: Just as earlier studies have shown for television viewing, cell phone use might be a risk factor related to being overweight among children.

DOI： 10.1089/chi.2018.0312

A risk score predicting new incidence of hypertension in Japan Reviewed International journal

Kadomatsu Yuka, Tsukamoto Mineko, Sasakabe Tae, Kawai Sayo, Naito Mariko, Kubo Yoko, Okada Rieko, Tamura Takashi, Hishida Asahi, Mori Atsuyoshi, Hamajima Nobuyuki, Yokoi Kohei, Wakai Kenji

JOURNAL OF HUMAN HYPERTENSION Vol. 33 ( 10 ) page： 748 - 755 2019.10

Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Human Hypertension

The prevention of hypertension starts with the awareness of risk. Our aim was to construct a simple and well-validated risk model for nonhypertensive people in Japan consisting of basic clinical variables, using a dataset for two areas derived from the Japan Multi-Institutional Collaborative Cohort Study. We constructed a continuous-value model using data on 5105 subjects participating in both the baseline survey and a second survey conducted after 5 years. The area under the receiver operating characteristic curve (AUC) and the Hosmer–Lemeshow χ2 statistic for the entire cohort were 0.826 and 7.06, respectively. For validation, the entire cohort was randomly divided 100 times into derivation and validation sets at a ratio of 6:4. The summarized median AUC and the Hosmer–Lemeshow χ2 statistic were 0.83 and 12.2, respectively. The AUC of a point-based model consisting of integer scores assigned to each variable was 0.826 and showed no difference, compared with the continuous-value model. This simple risk model may help the general population to assess their risks of new-onset hypertension.

DOI： 10.1038/s41371-019-0226-7