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Replication of 13 obesity loci among Singaporean Chinese, Malay and Asian-Indian populations

Dorajoo R, Blakemore AI, Sim X, Ong RT, Ng DP, Seielstad M, et al.

Int J Obes (Lond), 2012 Jan;36(1):159-63.
PMID: 21544081 DOI: 10.1038/ijo.2011.86

Recent genome-wide association studies (GWAS) have identified 38 obesity-associated loci among European populations. However, their contribution to obesity in other ethnicities is largely unknown.
Polymorphisms identified through genome-wide association studies and their associations with type 2 diabetes in Chinese, Malays, and Asian-Indians in Singapore

Tan JT, Ng DP, Nurbaya S, Ye S, Lim XL, Leong H, et al.

J Clin Endocrinol Metab, 2010 Jan;95(1):390-7.
PMID: 19892838 DOI: 10.1210/jc.2009-0688

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 x 10(-4)], HHEX (OR = 1.15; P = 0.013), and KCNQ1 (OR = 1.21; P = 3 x 10(-4)) were significantly associated with T2DM. Among Malays, SNPs in CDKN2A/B (OR = 1.22; P = 3.7 x 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 x 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 x 10(-4)), CDKN2A/B (OR = 1.16; P = 9 x 10(-5)), HHEX (OR = 1.14; P = 6 x 10(-4)), and KCNQ1 (OR = 1.16-1.20; P = 3 x 10(-4) to 3 x 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.
Fulltext Genome-wide association study in a Chinese population identifies a susceptibility locus for type 2 diabetes at 7q32 near PAX4

Ma RC, Hu C, Tam CH, Zhang R, Kwan P, Leung TF, et al.

Diabetologia, 2013 Jun;56(6):1291-305.
PMID: 23532257 DOI: 10.1007/s00125-013-2874-4

AIMS/HYPOTHESIS: Most genetic variants identified for type 2 diabetes have been discovered in European populations. We performed genome-wide association studies (GWAS) in a Chinese population with the aim of identifying novel variants for type 2 diabetes in Asians.
METHODS: We performed a meta-analysis of three GWAS comprising 684 patients with type 2 diabetes and 955 controls of Southern Han Chinese descent. We followed up the top signals in two independent Southern Han Chinese cohorts (totalling 10,383 cases and 6,974 controls), and performed in silico replication in multiple populations.
RESULTS: We identified CDKN2A/B and four novel type 2 diabetes association signals with p

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