著者

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

出版者

Japan Epidemiological Association

雑誌

Journal of Epidemiology (ISSN:09175040)

巻号頁・発行日

pp.JE20220341, (Released:2023-07-29)

参考文献数

72

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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.