Genetic architecture of alcohol consumption identified by a genotype-stratified GWAS and impact on esophageal cancer risk in Japanese people
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- Yuriko N. Koyanagi
- Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
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- Masahiro Nakatochi
- Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
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- Shinichi Namba
- Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
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- Isao Oze
- Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
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- Hadrien Charvat
- Faculty of International Liberal Arts, Juntendo University, Tokyo, Japan.
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- Akira Narita
- Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
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- Takahisa Kawaguchi
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
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- Hiroaki Ikezaki
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan.
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- Asahi Hishida
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
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- Megumi Hara
- Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga, Japan.
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- Toshiro Takezaki
- Department of International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
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- Teruhide Koyama
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
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- Yohko Nakamura
- Cancer Prevention Center, Chiba Cancer Center Research Institute, Chiba, Japan.
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- Sadao Suzuki
- Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
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- Sakurako Katsuura-Kamano
- Department of Preventive Medicine, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
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- Kiyonori Kuriki
- Laboratory of Public Health, Division of Nutritional Sciences, School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan.
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- Yasuyuki Nakamura
- Department of Public Health, Shiga University of Medical Science, Otsu, Japan.
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- Kenji Takeuchi
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
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- Atsushi Hozawa
- Department of Preventive Medicine and Epidemiology, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
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- Kengo Kinoshita
- Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
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- Yoichi Sutoh
- Division of Biomedical Information Analysis, Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan.
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- Kozo Tanno
- Department of Hygiene and Preventive Medicine, School of Medicine, Iwate Medical University, Iwate, Japan.
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- Atsushi Shimizu
- Division of Biomedical Information Analysis, Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan.
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- Hidemi Ito
- Division of Cancer Information and Control, Department of Preventive Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
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- Yumiko Kasugai
- Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
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- Yukino Kawakatsu
- Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
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- Yukari Taniyama
- Division of Cancer Information and Control, Department of Preventive Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
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- Masahiro Tajika
- Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan.
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- Yasuhiro Shimizu
- Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.
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- Etsuji Suzuki
- Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
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- Yasuyuki Hosono
- Department of Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
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- Issei Imoto
- Aichi Cancer Center Research Institute, Nagoya, Japan.
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- Yasuharu Tabara
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
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- Meiko Takahashi
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
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- Kazuya Setoh
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
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- Koichi Matsuda
- Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
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- Shiori Nakano
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan.
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- Atsushi Goto
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan.
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- Ryoko Katagiri
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan.
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- Taiki Yamaji
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan.
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- Norie Sawada
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan.
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- Shoichiro Tsugane
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan.
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- Kenji Wakai
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
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- Masayuki Yamamoto
- Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
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- Makoto Sasaki
- Division of Ultrahigh Field MRI, Institute for Biomedical Sciences, Iwate Medical University, Iwate, Japan.
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- Fumihiko Matsuda
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
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- Yukinori Okada
- Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
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- Motoki Iwasaki
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan.
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- Paul Brennan
- Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.
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- Keitaro Matsuo
- Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
書誌事項
- 公開日
- 2024-01-26
- 資源種別
- journal article
- DOI
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- 10.1126/sciadv.ade2780
- 公開者
- American Association for the Advancement of Science (AAAS)
説明
<jats:p> An East Asian–specific variant on <jats:italic>aldehyde dehydrogenase 2</jats:italic> ( <jats:italic>ALDH2</jats:italic> rs671, G>A) is the major genetic determinant of alcohol consumption. We performed an rs671 genotype-stratified genome-wide association study meta-analysis of alcohol consumption in 175,672 Japanese individuals to explore gene-gene interactions with rs671 behind drinking behavior. The analysis identified three genome-wide significant loci ( <jats:italic>GCKR</jats:italic> , <jats:italic>KLB</jats:italic> , and <jats:italic>ADH1B</jats:italic> ) in wild-type homozygotes and six ( <jats:italic>GCKR</jats:italic> , <jats:italic>ADH1B</jats:italic> , <jats:italic>ALDH1B1</jats:italic> , <jats:italic>ALDH1A1</jats:italic> , <jats:italic>ALDH2</jats:italic> , and <jats:italic>GOT2</jats:italic> ) in heterozygotes, with five showing genome-wide significant interaction with rs671. Genetic correlation analyses revealed ancestry-specific genetic architecture in heterozygotes. Of the discovered loci, four ( <jats:italic>GCKR</jats:italic> , <jats:italic>ADH1B</jats:italic> , <jats:italic>ALDH1A1</jats:italic> , and <jats:italic>ALDH2</jats:italic> ) were suggested to interact with rs671 in the risk of esophageal cancer, a representative alcohol-related disease. Our results identify the genotype-specific genetic architecture of alcohol consumption and reveal its potential impact on alcohol-related disease risk. </jats:p>
収録刊行物
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- Science Advances
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Science Advances 10 (4), 2024-01-26
American Association for the Advancement of Science (AAAS)
- Tweet
詳細情報 詳細情報について
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- CRID
- 1360021391875839744
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- ISSN
- 23752548
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- 資料種別
- journal article
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- データソース種別
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- Crossref
- KAKEN
- OpenAIRE
