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
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- Tsukamoto Mineko
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine
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- Hishida Asahi
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine
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- Tamura Takashi
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine
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- Nagayoshi Mako
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine
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- Okada Rieko
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine
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- Kubo Yoko
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine
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- Kato Yasufumi
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine
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- Hamajima Nobuyuki
- Department of Healthcare Administration, Nagoya University Graduate School of Medicine
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- Nishida Yuichiro
- Department of Preventive Medicine, Faculty of Medicine, Saga University
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- Shimanoe Chisato
- Department of Pharmacy, Saga University Hospital
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- Ibusuki Rie
- Department of International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences
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- Shibuya Kenichi
- Department of International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences
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- Takashima Naoyuki
- Department of Public Health, Shiga University of Medical Science
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- Nakamura Yasuyuki
- Department of Public Health, Shiga University of Medical Science
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- Kusakabe Miho
- Cancer Prevention Center, Chiba Cancer Center Research Institute
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- Nakamura Yohko
- Cancer Prevention Center, Chiba Cancer Center Research Institute
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- Koyanagi Yuriko N.
- Division of Cancer Information and Control, Department of Preventive Medicine, Aichi Cancer Center Research Institute
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- Oze Isao
- Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute
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- Nishiyama Takeshi
- Department of Public Health, Nagoya City University Graduate School of Medical Sciences
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- Suzuki Sadao
- Department of Public Health, Nagoya City University Graduate School of Medical Sciences
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- Watanabe Isao
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine
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- Matsui Daisuke
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine
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- Otonari Jun
- Department of Psychosomatic Medicine, Kyushu University Graduate School of Medical Sciences, Faculty of Medical Sciences
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- Ikezaki Hiroaki
- Department of Comprehensive General Internal Medicine, Kyushu University Graduate School of Medical Sciences, Faculty of Medical Sciences
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- Katsuura-Kamano Sakurako
- Department of Preventive Medicine, Tokushima University Graduate School of Biomedical Sciences
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- Arisawa Kokichi
- Laboratory of Public Health, Division of Nutritional Sciences, School of Food and Nutritional Sciences, University of Shizuoka
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- Kuriki Kiyonori
- Laboratory of Public Health, Division of Nutritional Sciences, School of Food and Nutritional Sciences, University of Shizuoka
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- Nakatochi Masahiro
- Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine
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- Momozawa Yukihide
- Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences
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- Takeuchi Kenji
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine Department of International and Community Oral Health, Tohoku University Graduate School of Dentistry
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- Wakai Kenji
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine
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- Matsuo Keitaro
- Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute Department of Epidemiology, Nagoya University Graduate School of Medicine
抄録
<p>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.</p><p>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.</p><p>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).</p><p>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.</p>
収録刊行物
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- Ｊｏｕｒｎａｌ ｏｆ Ｅｐｉｄｅｍｉｏｌｏｇｙ
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Ｊｏｕｒｎａｌ ｏｆ Ｅｐｉｄｅｍｉｏｌｏｇｙ 34 (5), 228-237, 2024-05-05
日本疫学会