- 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
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.