Genetic architecture of alcohol consumption identified by a genotype-stratified GWAS and impact on esophageal cancer risk in Japanese people-Reference-Cited by-同舟云学术

Genetic architecture of alcohol consumption identified by a genotype-stratified GWAS and impact on esophageal cancer risk in Japanese people

Published:2024-01-26 Issue:4 Volume:10 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Koyanagi Yuriko N.¹^ORCID,Nakatochi Masahiro²^ORCID,Namba Shinichi³^ORCID,Oze Isao¹^ORCID,Charvat Hadrien⁴⁵⁶,Narita Akira⁷^ORCID,Kawaguchi Takahisa⁸^ORCID,Ikezaki Hiroaki⁹¹⁰^ORCID,Hishida Asahi¹¹^ORCID,Hara Megumi¹²^ORCID,Takezaki Toshiro¹³^ORCID,Koyama Teruhide¹⁴^ORCID,Nakamura Yohko¹⁵^ORCID,Suzuki Sadao¹⁶^ORCID,Katsuura-Kamano Sakurako¹⁷^ORCID,Kuriki Kiyonori¹⁸^ORCID,Nakamura Yasuyuki¹⁹,Takeuchi Kenji¹¹²⁰²¹^ORCID,Hozawa Atsushi²²^ORCID,Kinoshita Kengo⁷^ORCID,Sutoh Yoichi²³^ORCID,Tanno Kozo²⁴²⁵^ORCID,Shimizu Atsushi²³²⁶^ORCID,Ito Hidemi²⁷²⁸^ORCID,Kasugai Yumiko¹²⁹^ORCID,Kawakatsu Yukino¹^ORCID,Taniyama Yukari²⁷^ORCID,Tajika Masahiro³⁰^ORCID,Shimizu Yasuhiro³¹,Suzuki Etsuji³²³³,Hosono Yasuyuki³⁴,Imoto Issei³⁵^ORCID,Tabara Yasuharu⁸³⁶,Takahashi Meiko⁸^ORCID,Setoh Kazuya⁸, ,Matsuda Koichi³⁷^ORCID,Nakano Shiori³⁸^ORCID,Goto Atsushi³⁸³⁹^ORCID,Katagiri Ryoko⁴⁰⁴¹^ORCID,Yamaji Taiki³⁸^ORCID,Sawada Norie⁴⁰^ORCID,Tsugane Shoichiro⁴⁰⁴¹^ORCID,Wakai Kenji¹¹,Yamamoto Masayuki⁷^ORCID,Sasaki Makoto⁴²⁴³^ORCID,Matsuda Fumihiko⁸^ORCID,Okada Yukinori³⁴⁴⁴⁵⁴⁶⁴⁷^ORCID,Iwasaki Motoki³⁸⁴⁰^ORCID,Brennan Paul⁴⁸^ORCID,Matsuo Keitaro¹²⁹^ORCID

Affiliation:

1. Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.

2. Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.

3. Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.

4. Faculty of International Liberal Arts, Juntendo University, Tokyo, Japan.

5. Division of International Health Policy Research, Institute for Cancer Control, National Cancer Center, Tokyo, Japan.

6. Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France.

7. Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.

8. Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.

9. Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan.

10. Department of Comprehensive General Internal Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.

11. Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.

12. Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga, Japan.

13. Department of International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.

14. Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.

15. Cancer Prevention Center, Chiba Cancer Center Research Institute, Chiba, Japan.

16. Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

17. Department of Preventive Medicine, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.

18. Laboratory of Public Health, Division of Nutritional Sciences, School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan.

19. Department of Public Health, Shiga University of Medical Science, Otsu, Japan.

20. Department of International and Community Oral Health, Tohoku University Graduate School of Dentistry, Sendai, Japan.

21. Division for Regional Community Development, Liaison Center for Innovative Dentistry, Tohoku University Graduate School of Dentistry, Sendai, Japan.

22. Department of Preventive Medicine and Epidemiology, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.

23. Division of Biomedical Information Analysis, Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan.

24. Department of Hygiene and Preventive Medicine, School of Medicine, Iwate Medical University, Iwate, Japan.

25. Division of Clinical Research and Epidemiology, Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan.

26. Division of Biomedical Information Analysis, Institute for Biomedical Sciences, Iwate Medical University, Iwate, Japan.

27. Division of Cancer Information and Control, Department of Preventive Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.

28. Department of Descriptive Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

29. Department of Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

30. Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan.

31. Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

32. Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.

33. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

34. Department of Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.

35. Aichi Cancer Center Research Institute, Nagoya, Japan.

36. Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan.

37. Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.

38. Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan.

39. Department of Health Data Science, Graduate School of Data Science, Yokohama City University, Yokohama, Japan.

40. Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan.

41. National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Tokyo, Japan.

42. Division of Ultrahigh Field MRI, Institute for Biomedical Sciences, Iwate Medical University, Iwate, Japan.

43. Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan.

44. Department of Genome Informatics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

45. Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.

46. Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan.

47. Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Japan.

48. Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.

Abstract

An East Asian–specific variant on aldehyde dehydrogenase 2 ( ALDH2 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 ( GCKR , KLB , and ADH1B ) in wild-type homozygotes and six ( GCKR , ADH1B , ALDH1B1 , ALDH1A1 , ALDH2 , and GOT2 ) 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 ( GCKR , ADH1B , ALDH1A1 , and ALDH2 ) 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.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/sciadv.ade2780

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