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Transferability of type 2 diabetes implicated loci in multi-ethnic cohorts from Southeast Asia.

Publication ,  Journal Article
Sim, X; Ong, RT-H; Suo, C; Tay, W-T; Liu, J; Ng, DP-K; Boehnke, M; Chia, K-S; Wong, T-Y; Seielstad, M; Teo, Y-Y; Tai, E-S
Published in: PLoS Genet
April 2011

Recent large genome-wide association studies (GWAS) have identified multiple loci which harbor genetic variants associated with type 2 diabetes mellitus (T2D), many of which encode proteins not previously suspected to be involved in the pathogenesis of T2D. Most GWAS for T2D have focused on populations of European descent, and GWAS conducted in other populations with different ancestry offer a unique opportunity to study the genetic architecture of T2D. We performed genome-wide association scans for T2D in 3,955 Chinese (2,010 cases, 1,945 controls), 2,034 Malays (794 cases, 1,240 controls), and 2,146 Asian Indians (977 cases, 1,169 controls). In addition to the search for novel variants implicated in T2D, these multi-ethnic cohorts serve to assess the transferability and relevance of the previous findings from European descent populations in the three major ethnic populations of Asia, comprising half of the world's population. Of the SNPs associated with T2D in previous GWAS, only variants at CDKAL1 and HHEX/IDE/KIF11 showed the strongest association with T2D in the meta-analysis including all three ethnic groups. However, consistent direction of effect was observed for many of the other SNPs in our study and in those carried out in European populations. Close examination of the associations at both the CDKAL1 and HHEX/IDE/KIF11 loci provided some evidence of locus and allelic heterogeneity in relation to the associations with T2D. We also detected variation in linkage disequilibrium between populations for most of these loci that have been previously identified. These factors, combined with limited statistical power, may contribute to the failure to detect associations across populations of diverse ethnicity. These findings highlight the value of surveying across diverse racial/ethnic groups towards the fine-mapping efforts for the casual variants and also of the search for variants, which may be population-specific.

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Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

April 2011

Volume

7

Issue

4

Start / End Page

e1001363

Location

United States

Related Subject Headings

  • tRNA Methyltransferases
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Linkage Disequilibrium
  • Kinesins
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Genetic Loci
 

Citation

APA
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Sim, X., Ong, R.-H., Suo, C., Tay, W.-T., Liu, J., Ng, D.-K., … Tai, E.-S. (2011). Transferability of type 2 diabetes implicated loci in multi-ethnic cohorts from Southeast Asia. PLoS Genet, 7(4), e1001363. https://doi.org/10.1371/journal.pgen.1001363
Sim, Xueling, Rick Twee-Hee Ong, Chen Suo, Wan-Ting Tay, Jianjun Liu, Daniel Peng-Keat Ng, Michael Boehnke, et al. “Transferability of type 2 diabetes implicated loci in multi-ethnic cohorts from Southeast Asia.PLoS Genet 7, no. 4 (April 2011): e1001363. https://doi.org/10.1371/journal.pgen.1001363.
Sim X, Ong RT-H, Suo C, Tay W-T, Liu J, Ng DP-K, et al. Transferability of type 2 diabetes implicated loci in multi-ethnic cohorts from Southeast Asia. PLoS Genet. 2011 Apr;7(4):e1001363.
Sim, Xueling, et al. “Transferability of type 2 diabetes implicated loci in multi-ethnic cohorts from Southeast Asia.PLoS Genet, vol. 7, no. 4, Apr. 2011, p. e1001363. Pubmed, doi:10.1371/journal.pgen.1001363.
Sim X, Ong RT-H, Suo C, Tay W-T, Liu J, Ng DP-K, Boehnke M, Chia K-S, Wong T-Y, Seielstad M, Teo Y-Y, Tai E-S. Transferability of type 2 diabetes implicated loci in multi-ethnic cohorts from Southeast Asia. PLoS Genet. 2011 Apr;7(4):e1001363.

Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

April 2011

Volume

7

Issue

4

Start / End Page

e1001363

Location

United States

Related Subject Headings

  • tRNA Methyltransferases
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Linkage Disequilibrium
  • Kinesins
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Genetic Loci