4.8 Article

Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians

期刊

NATURE GENETICS
卷 44, 期 1, 页码 67-U97

出版社

NATURE PUBLISHING GROUP
DOI: 10.1038/ng.1019

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资金

  1. Ministry of Education, Culture, Sports, Science and Technology Japan
  2. National Institute of Biomedical Innovation Organization (NIBIO)
  3. Core Research for Evolutional Science and Technology (CREST) from the Japan Science Technology Agency
  4. National Center for Global Health and Medicine (NCGM)
  5. US National Institutes of Health [DK078150, TW05596, HL085144, TW008288, RR20649, ES10126, DK56350, R01CA124558, R01CA64277, R01CA70867, R01CA90899, R01CA100374, R01CA118229, R01CA92585, UL1 RR024975, DK58845, HG004399]
  6. Hong Kong Government Research Grants Council [CUHK 1/04C, CUHK4724/07M]
  7. Government of the Hong Kong Special Administrative Region [ITS/487/09FP]
  8. Korea Centers for Disease Control and Prevention [4845-301, 4851-302, 4851-307]
  9. Korea National Institute of Health, the Republic of Korea [2011-N73005-00]
  10. National Science Council of Taiwan [NSC99-3112-B-002-019]
  11. National Genotyping Center of National Research Program for Genomic Medicine, Taiwan [NSC98-3112-B-001-037]
  12. Department of Defense [BC050791]
  13. Vanderbilt Ingram
  14. Allen Foundation
  15. National 973 Program [2011CB504001]
  16. National Natural Science Foundation of China [30800617]
  17. Shanghai Rising-Star Program, China [09QA1404400]
  18. National 863 Program [2006AA02A409]
  19. Shanghai Municipality for Basic Research, China [08dj1400601]
  20. Ministry of Health Welfare [00-PJ3-PG6-GN07-001]
  21. Ministry of Education, Science and Technology (MEST)
  22. National Research Foundation (NRF), Korea [R31-2008-000-10103-0]
  23. Biomedical Research Council of Singapore [BMRC05/1/36/19/413, 03/1/27/18/216]
  24. National Medical Research Council of Singapore [NMRC/1174/2008]
  25. National Medical Research Council [NMRC/CSA/008/2009, NMRC0796/2003, NMRC/STaR/0003/2008]
  26. Biomedical Research Council (BMRC) [09/1/35/19/616]
  27. Singapore National Research Foundation [NRF-RF-2010-05]
  28. MRC [G0900339] Funding Source: UKRI
  29. Medical Research Council [G0600717B, MC_U106179471, G0900339] Funding Source: researchfish
  30. Grants-in-Aid for Scientific Research [24591347, 21390209, 23390247, 20229008, 21591124] Funding Source: KAKEN

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We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression(1,2), is known for its association with fasting glucose levels(3,4). The evidence of an association with T2D for PEPD(5) and HNF4A(6,7) has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.

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