Journal of Epidemiology (May 2024)
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
- 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
Affiliations
- Mineko Tsukamoto
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Asahi Hishida
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Takashi Tamura
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Mako Nagayoshi
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Rieko Okada
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Yoko Kubo
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Yasufumi Kato
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Nobuyuki Hamajima
- Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Yuichiro Nishida
- Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga, Japan
- Chisato Shimanoe
- Department of Pharmacy, Saga University Hospital, Saga, Japan
- Rie Ibusuki
- Department of International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
- Kenichi Shibuya
- Department of International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
- Naoyuki Takashima
- Department of Public Health, Shiga University of Medical Science, Otsu, Japan
- Yasuyuki Nakamura
- Department of Public Health, Shiga University of Medical Science, Otsu, Japan
- Miho Kusakabe
- Cancer Prevention Center, Chiba Cancer Center Research Institute, Chiba, Japan
- Yohko Nakamura
- Cancer Prevention Center, Chiba Cancer Center Research Institute, Chiba, Japan
- Yuriko N. Koyanagi
- Division of Cancer Information and Control, Department of Preventive Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan
- Isao Oze
- Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan
- Takeshi Nishiyama
- Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
- Sadao Suzuki
- Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
- Isao Watanabe
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Daisuke Matsui
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Jun Otonari
- Department of Psychosomatic Medicine, Kyushu University Graduate School of Medical Sciences, Faculty of Medical Sciences, Fukuoka, Japan
- Hiroaki Ikezaki
- Department of Comprehensive General Internal Medicine, Kyushu University Graduate School of Medical Sciences, Faculty of Medical Sciences, Fukuoka, Japan
- Sakurako Katsuura-Kamano
- Department of Preventive Medicine, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
- Kokichi Arisawa
- Laboratory of Public Health, Division of Nutritional Sciences, School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan
- Kiyonori Kuriki
- Laboratory of Public Health, Division of Nutritional Sciences, School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan
- Masahiro Nakatochi
- Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Yukihide Momozawa
- Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
- Kenji Takeuchi
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Kenji Wakai
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Keitaro Matsuo
- Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan
- DOI
- https://doi.org/10.2188/jea.JE20220341
- Journal volume & issue
-
Vol. 34,
no. 5
pp. 228 – 237
Abstract
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 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). Conclusion: 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 cardiovascular disease prevention.
Keywords
- genome-wide association study
- folate metabolism
- gene–environment interaction
- cardiovascular disease prevention
