期刊
DIABETOLOGIA
卷 56, 期 12, 页码 2619-2628出版社
SPRINGER
DOI: 10.1007/s00125-013-3047-1
关键词
Ethnic difference; Genetic association; Type 2 diabetes
资金
- National Institutes of Health, USA [HL087647, HL088457, EY014684, DK079888]
- ARRA Supplement [EY014684-03S1, EY014684-04S1]
- National Health Research Institutes, Taiwan [PH-100-SP-01, BS-094-PP-01, PH-100-PP-03]
- National Science Council, Taiwan [NSC 98-2314-B-075A-002-MY3, NSC 96-2314-B-002-151, NSC 96-2314-B-002-152, NSC 98-2314-B-002-122MY2, NSC 100-2314-B-002-115, NSC 101-2325-002-078, 101-2314-B-075A-006-MY3]
- Taichung Veterans General Hospital, Taiwan [TCVGH-1013001C, TCVGH-1013002D]
- National Taiwan University Hospital, Taiwan [NTUH 98-N1266, NTUH 100-N1775, NTUH 101-N2010, NTUH 101-N, VN101-04, NTUH 101-S1784]
- UCLA/Cedars-Sinai/Harbor/Drew Clinical and Translational Science Institute (CTSI) [UL1 TR000124-01]
- Southern California Diabetes Research Grant (DRC) [DK063491]
- Cedars-Sinai Board of Governor's Chair in Medical Genetics
- Cedars-SinaiWinnick Clinical Scholars Award
Candidate gene and genome-wide association studies have identified similar to 60 susceptibility loci for type 2 diabetes. A majority of these loci have been discovered and tested only in European populations. The aim of this study was to assess the presence and extent of trans-ethnic effects of these loci in an East Asian population. A total of 9,335 unrelated Chinese Han individuals, including 4,535 with type 2 diabetes and 4,800 non-diabetic ethnically matched controls, were genotyped using the Illumina 200K Metabochip. We tested 50 established loci for type 2 diabetes and related traits (fasting glucose, fasting insulin, 2 h glucose). Disease association with the additive model of inheritance was analysed with logistic regression. We found that 14 loci significantly transferred to the Chinese population, with two loci (p = 5.7 x 10(-12) for KCNQ1; p = 5.0 x 10(-8) for CDKN2A/B-CDKN2BAS) reaching independent genome-wide statistical significance. Five of these 14 loci had similar lead single-nucleotide polymorphisms (SNPs) as were found in the European studies while the other nine were different. Further stepwise conditional analysis identified a total of seven secondary signals and an independent novel locus at the 3' end of CDKAL1. These results suggest that many loci associated with type 2 diabetes are commonly shared between European and Chinese populations. Identification of population-specific SNPs may increase our understanding of the genetic architecture underlying type 2 diabetes in different ethnic populations.
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