研究者詳細 - 田村　高志

論文 - 田村　高志

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A genome-wide association study in Japanese identified one variant associated with a preference for a Japanese dietary pattern 査読有り国際誌

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 75 巻 ( 6 ) 頁： 937 - 945 2021年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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 査読有り国際誌

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 84 巻頁： 111114 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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 査読有り国際誌

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 112 巻 ( 4 ) 頁： 1579 - 1588 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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 査読有り国際誌

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 75 巻 ( 3 ) 頁： 480 - 488 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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 査読有り国際誌

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 34 巻 ( 2 ) 頁： 293 - 299 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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. 査読有り

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年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：日本疫学会

<p><b>Background:</b> 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.</p><p><b>Methods:</b> 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): IV<sub>CRP</sub> and IV<sub>Asian</sub>, based on SNPs previously identified in European and Asian populations. IV<sub>CRP</sub> and IV<sub>Asian</sub> explained 3.4% and 3.9% of the variation in hs-CRP, respectively.</p><p><b>Results:</b> Using the IV<sub>CRP</sub>, 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 IV<sub>Asian</sub>, 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 (IV<sub>CRP</sub>: −0.008; 95% CI, −0.058 to 0.042; IV<sub>Asian</sub>: 0.001; 95% CI, −0.036 to 0.036).</p><p><b>Conclusions:</b> Our two-sample MR analyses with different IVs did not support a causal effect of hs-CRP on eGFR.</p>

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 査読有り

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 83 巻 ( 1 ) 頁： 183 - 194 2021年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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 査読有り

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

JOURNAL OF EPIDEMIOLOGY 31 巻 ( 1 ) 頁： 12 - 20 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Epidemiology

Background: While duodenal ulcer (DU) and gastric cancer (GC) are both H. pylori infection-related diseases, individuals withDU 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: Six PSCA 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 (CIs) for the 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 査読有り国際誌

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 762 巻頁： 145019 2020年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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 査読有り国際誌

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 89 巻頁： 129 - 138 2020年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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 査読有り国際誌

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 10 巻 ( 1 ) 頁： 18499 2020年10月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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. 査読有り

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年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：日本疫学会

<p><b>Background:</b> 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.</p><p><b>Methods:</b> 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.</p><p><b>Results:</b> 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.</p><p><b>Conclusions:</b> 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.</p>

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 査読有り国際誌

Arisawa, K; Katsuura-Kamano, S; Uemura, H; Tien, NV; Hishida, A; Tamura, T; Kubo, Y; Tsukamoto, M; Tanaka, K; Hara, M; Takezaki, T; Nishimoto, D; Koyama, T; Ozaki, E; Suzuki, S; Nishiyama, T; Kuriki, K; Kadota, A; Takashima, N; Ikezaki, H; Murata, M; Oze, I; Matsuo, K; Mikami, H; Nakamura, Y; Takeuchi, K; Wakai, K

NUTRIENTS 12 巻 ( 6 ) 2020年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Nutrients

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 査読有り国際誌

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 2020 巻頁： 7591263 2020年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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 査読有り国際誌

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 79 巻 ( 5 ) 頁： 657 - 665 2020年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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 査読有り国際誌

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 34 巻 ( 2 ) 頁： 125 - 131 2020年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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 査読有り国際誌

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

NUTRITION JOURNAL 19 巻 ( 1 ) 頁： 2 - 2 2020年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Nutrition 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 査読有り国際誌

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 79 巻 ( 1 ) 頁： 164 - 166 2020年1月

Sedentary Time is Associated with Cardiometabolic Diseases in A Large Japanese Population: A Cross-Sectional Study 査読有り国際誌

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 27 巻 ( 10 ) 頁： 1097 - 1107 2020年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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 査読有り国際誌

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 15 巻 ( 7 ) 頁： 417 - 425 2019年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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

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