Genome-Wide Association Meta-analysis Identifies Novel Variants Associated With Fasting Plasma Glucose in East Asians

Author:

Hwang Joo-Yeon1,Sim Xueling23,Wu Ying4,Liang Jun5,Tabara Yasuharu6,Hu Cheng7,Hara Kazuo89,Tam Claudia H.T.10,Cai Qiuyin11,Zhao Qi12,Jee Sunha13,Takeuchi Fumihiko14,Go Min Jin1,Ong Rick Twee Hee15,Ohkubo Takayoshi1617,Kim Young Jin1,Zhang Rong7,Yamauchi Toshimasa8,So Wing Yee10,Long Jirong11,Gu Dongfeng181920,Lee Nanette R.21,Kim Soriul13,Katsuya Tomohiro22,Oh Ji Hee1,Liu Jianjun23,Umemura Satoshi24,Kim Yeon-Jung1,Jiang Feng7,Maeda Shiro25,Chan Juliana C.N.10,Lu Wei26,Hixson James E.27,Adair Linda S.28,Jung Keum Ji13,Nabika Toru29,Bae Jae-Bum1,Lee Mi Hee1,Seielstad Mark30,Young Terri L.31,Teo Yik Ying315233233,Kita Yoshikuni17,Takashima Naoyuki17,Osawa Haruhiko34,Lee So-Hyun1,Shin Min-Ho35,Shin Dong Hoon36,Choi Bo Youl37,Shi Jiajun11,Gao Yu-Tang38,Xiang Yong-Bing38,Zheng Wei11,Kato Norihiro14,Yoon Miwuk13,He Jiang12,Shu Xiao Ou11,Ma Ronald C.W.10,Kadowaki Takashi8,Jia Weiping7,Miki Tetsuro39,Qi Lu5,Tai E Shyong144041,Mohlke Karen L.4,Han Bok-Ghee1,Cho Yoon Shin42,Kim Bong-Jo1

Affiliation:

1. Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Republic of Korea

2. Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI

3. Centre for Molecular Epidemiology, National University of Singapore, Singapore, Singapore

4. Department of Genetics, University of North Carolina, Chapel Hill, NC

5. Department of Nutrition, Harvard School of Public Health, Boston, MA

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

7. Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China

8. Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

9. Department of Integrated Molecular Science on Metabolic Diseases, 22nd Century Medical and Research Center, The University of Tokyo, Tokyo, Japan

10. Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong

11. Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center; and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN

12. Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA

13. Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea

14. Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan

15. Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore

16. Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan

17. Department of Health Science, Shiga University of Medical Science, Shiga, Japan

18. State Key Laboratory of Cardiovascular Disease, Department of Epidemiology, National Center for Cardiovascular Diseases, Beijing, China

19. Population Genetics, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences, Beijing, China

20. Peking Union Medical College, Beijing, China

21. Office of Population Studies Foundation, University of San Carlos, Cebu City, Philippines

22. Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Suita, Japan

23. Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore

24. Department of Medical Science and Cardiorenal Medicine, Yokohama City University School of Medicine, Yokohama, Japan

25. Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

26. Shanghai Municipal Center for Disease Control & Prevention, Shanghai, China

27. Human Genetics Center, The University of Texas School of Public Health, Houston, TX

28. Department of Nutrition, University of North Carolina, Chapel Hill, NC

29. Department of Functional Pathology, Shimane University School of Medicine, Izumo, Japan

30. Institute for Human Genetics, University of California, San Francisco, San Francisco, CA

31. Center for Human Genetics, Duke University Medical Center, Durham, NC

32. Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore

33. Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, Singapore

34. Department of Molecular and Genetic Medicine, Ehime University Graduate School of Medicine, Toon, Japan

35. Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, South Korea

36. Department of Occupational and Environmental Medicine, Keimyung University Dongsan Medical Center, Daegu, South Korea

37. Department of Preventive Medicine, College of Medicine, Hanyang University, Seoul, Korea

38. Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

39. Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Toon, Japan

40. Department of Medicine, National University of Singapore, Singapore, Singapore

41. Duke-National University of Singapore Graduate Medical School, Singapore, Singapore

42. Department of Biomedical Science, Hallym University, Chuncheon, Korea

Abstract

Fasting plasma glucose (FPG) has been recognized as an important indicator for the overall glycemic state preceding the onset of metabolic diseases. So far, most indentified genome-wide association loci for FPG were derived from populations with European ancestry, with a few exceptions. To extend a thorough catalog for FPG loci, we conducted meta-analyses of 13 genome-wide association studies in up to 24,740 nondiabetic subjects with East Asian ancestry. Follow-up replication analyses in up to an additional 21,345 participants identified three new FPG loci reaching genome-wide significance in or near PDK1-RAPGEF4, KANK1, and IGF1R. Our results could provide additional insight into the genetic variation implicated in fasting glucose regulation.

Publisher

American Diabetes Association

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

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