Logo image
Identification of new genetic risk variants for type 2 diabetes
Journal article   Open access   Peer reviewed

Identification of new genetic risk variants for type 2 diabetes

Xiao Ou Shu, Jirong Long, Qiuyin Cai, Lu Qi, Yong-Bing Xiang, Yoon Shin Cho, E Shyong Tai, Xu Lin, Wong-Ho Chow, Min Jin Go, …
PLoS genetics, Vol.6(9), pp.e1001127-e1001127
09/16/2010
DOI: 10.1371/journal.pgen.1001127
PMCID: PMC2940731
PMID: 20862305
url
https://doi.org/10.1371/journal.pgen.1001127View
Published (Version of record) Open Access

Abstract

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.
China Genetic Predisposition to Disease Chromosomes, Human - genetics Diabetes Mellitus, Type 2 - genetics Humans Middle Aged Risk Factors Asian Continental Ancestry Group - genetics Male Alleles Polymorphism, Single Nucleotide - genetics Female Odds Ratio

Details

Metrics

Logo image