Polymorphisms Identified through Genome-Wide Association Studies and Their Associations with Type 2 Diabetes in Chinese, Malays, and Asian-Indians in Singapore

Context: Novel type 2 diabetes mellitus (T2DM) susceptibility loci, identified through genome-wide association studies (GWAS), have been replicated in many European and Japanese populations. However, the association in other East Asian populations is less well characterized. Objective: To examine th...

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Bibliographic Details
Published in:The journal of clinical endocrinology and metabolism 2010-01, Vol.95 (1), p.390-397
Main Authors: Tan, Jonathan T, Ng, Daniel P. K, Nurbaya, Siti, Ye, Sandra, Lim, Xiu Li, Leong, Helen, Seet, Lin Tze, Siew, Wei Fong, Kon, Winston, Wong, Tien Yin, Saw, Seang Mei, Aung, Tin, Chia, Kee Seng, Lee, Jeannette, Chew, Suok Kai, Seielstad, Mark, Tai, E. Shyong
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Asian Continental Ancestry Group - genetics
Biological and medical sciences
Case-Control Studies
Cohort Studies
Diabetes Mellitus, Type 2 - ethnology
Diabetes Mellitus, Type 2 - genetics
Diabetes. Impaired glucose tolerance
DNA Mutational Analysis - methods
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Feeding. Feeding behavior
Fundamental and applied biological sciences. Psychology
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
India - ethnology
Malaysia - ethnology
Medical sciences
Meta-Analysis as Topic
Middle Aged
Polymorphism, Single Nucleotide - physiology
Singapore
Vertebrates: anatomy and physiology, studies on body, several organs or systems
Vertebrates: endocrinology
Young Adult
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Summary:Context: Novel type 2 diabetes mellitus (T2DM) susceptibility loci, identified through genome-wide association studies (GWAS), have been replicated in many European and Japanese populations. However, the association in other East Asian populations is less well characterized. Objective: To examine the effects of SNPs in CDKAL1, CDKN2A/B, IGF2BP2, HHEX, SLC30A8, PKN2, LOC387761, and KCNQ1 on risk of T2DM in Chinese, Malays, and Asian-Indians in Singapore. Design: We genotyped these candidate single-nucleotide polymorphisms (SNPs) in subjects from three major ethnic groups in Asia, namely, the Chinese (2196 controls and 1541 cases), Malays (2257 controls and 1076 cases), and Asian-Indians (364 controls and 246 cases). We also performed a metaanalysis of our results with published studies in East Asians. Results: In Chinese, SNPs in CDKAL1 [odds ratio (OR) = 1.19; P = 2 × 10−4], HHEX (OR = 1.15; P = 0.013), and KCNQ1 (OR = 1.21; P = 3 × 10−4) were significantly associated with T2DM. Among Malays, SNPs in CDKN2A/B (OR = 1.22; P = 3.7 × 10−4), HHEX (OR = 1.12; P = 0.044), SLC30A8 (OR = 1.12; P = 0.037), and KCNQ1 (OR = 1.19–1.25; P = 0.003–2.5 × 10−4) showed significant association with T2DM. The combined analysis of the three ethnic groups revealed significant associations between SNPs in CDKAL1 (OR = 1.13; P = 3 × 10−4), CDKN2A/B (OR = 1.16; P = 9 × 10−5), HHEX (OR = 1.14; P = 6 × 10−4), and KCNQ1 (OR = 1.16–1.20; P = 3 × 10−4 to 3 × 10−6) with T2DM. SLC30A8 (OR = 1.06; P = 0.039) showed association only after adjustment for gender and body mass index. Metaanalysis with data from other East Asian populations showed similar effect sizes to those observed in populations of European ancestry. Conclusions: SNPs at T2DM susceptibility loci identified through GWAS in populations of European ancestry show similar effects in Asian populations. Failure to detect these effects across different populations may be due to issues of power owing to limited sample size, lower minor allele frequency, or differences in genetic effect sizes. Combined data from multiple Asian populations show that common variants associated with type 2 diabetes, identified in populations of European ancestry, are also associated in East Asians.
ISSN:0021-972X
1945-7197
DOI:10.1210/jc.2009-0688