Identification of new genetic risk variants for type 2 diabetes.
Although more than 20 genetic susceptibility loci have been reported for type 2 diabetes (T2D), most reported variants have small to moderate effects and account for only a small proportion of the heritability of T2D, suggesting that the majority of inter-person genetic variation in this disease remains to be determined. We conducted a multistage, genome-wide association study (GWAS) within the Asian Consortium of Diabetes to search for T2D susceptibility markers. From 590,887 SNPs genotyped in 1,019 T2D cases and 1,710 controls selected from Chinese women in Shanghai, we selected the top 2,100 SNPs that were not in linkage disequilibrium (r(2)<0.2) with known T2D loci for in silico replication in three T2D GWAS conducted among European Americans, Koreans, and Singapore Chinese. The 5 most promising SNPs were genotyped in an independent set of 1,645 cases and 1,649 controls from Shanghai, and 4 of them were further genotyped in 1,487 cases and 3,316 controls from 2 additional Chinese studies. Consistent associations across all studies were found for rs1359790 (13q31.1), rs10906115 (10p13), and rs1436955 (15q22.2) with P-values (per allele OR, 95%CI) of 6.49 × 10(-9) (1.15, 1.10-1.20), 1.45 × 10(-8) (1.13, 1.08-1.18), and 7.14 × 10(-7) (1.13, 1.08-1.19), respectively, in combined analyses of 9,794 cases and 14,615 controls. Our study provides strong evidence for a novel T2D susceptibility locus at 13q31.1 and the presence of new independent risk variants near regions (10p13 and 15q22.2) reported by previous GWAS.
Shu
Xiao Ou
XO
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. xiao-ou.shu@vanderbilt.edu
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Yong-Bing
YB
Cho
Yoon Shin
YS
Tai
E Shyong
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Xiangyang
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Lin
Xu
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Chow
Wong-Ho
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Min Jin
MJ
Seielstad
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Bao
Wei
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Huaixing
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Cornelis
Marilyn C
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Yu
Kai
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Wen
Wanqing
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Shi
Jiajun
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Han
Bok-Ghee
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Sim
Xue Ling
XL
Liu
Liegang
L
Qi
Qibin
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Kim
Hyung-Lae
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Daniel P K
DP
Lee
Jong-Young
JY
Kim
Young Jin
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Yu-Tang
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Frank B
FB
D000483:Alleles; D044466:Asian People / Q000235:genetics; D002681:China; D002877:Chromosomes, Human / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors