期刊
DIABETES
卷 62, 期 1, 页码 291-298出版社
AMER DIABETES ASSOC
DOI: 10.2337/db12-0454
关键词
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资金
- National High Technology Research and Development Program of China (863 Program) [2009AA022704]
- National Basic Research Program of China (973 Program) [2011CB504002]
- National Natural Science Foundation of China [81021002, 81170734, 81170735]
- Chinese Academy of Sciences [KSCX2-EW-R-10]
- Medical Research Council [MC_U106188470] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0611-10219] Funding Source: researchfish
- Grants-in-Aid for Scientific Research [23591327] Funding Source: KAKEN
- MRC [MC_UU_12015/4, MC_U106188470] Funding Source: UKRI
Substantial progress has been made in identification of type 2 diabetes (T2D) risk loci in the past few years, but our understanding of the genetic basis of T2D in ethnically diverse populations remains limited. We performed a genome-wide association study and a replication study in Chinese Hans comprising 8,569 T2D case subjects and 8,923 control subjects in total, from which 10 single nucleotide polymorphisms were selected for further follow-up in a de novo replication sample of 3,410 T2D case and 3,412 control subjects and an in silico replication sample of 6,952 T2D case and 11,865 control subjects. Besides confirming seven established T2D loci (CDKAL1, CDKN2A/B, KCNQ1, CDC123, GLIS3, HNF1B, and DUSP9) at genome-wide significance, we identified two novel T2D loci, including G-protein-coupled receptor kinase 5 (GRK5) (rs10886471: P = 7.1 x 10(-9)) and RASGRP1 (rs7403531: P = 3.9 x 10-9), of which the association signal at GRK5 seems to be specific to East Asians. In nondiabetic individuals, the T2D risk-increasing allele of RASGRP1-rs7403531 was also associated with higher HbA(1c), and lower homeostasis model assessment of beta-cell function (P = 0.03 and 0.0209, respectively), whereas the T2D risk-increasing allele of GRK5-rs10886471 was also associated with higher fasting insulin (P = 0.0169) but not with fasting glucose. Our findings not only provide new insights into the pathophysiology of T2D, but may also shed light on the ethnic differences in T2D susceptibility. Diabetes 62:291-298, 2013
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