TY - JOUR
T1 - Identification of new genetic risk variants for Type 2 Diabetes
AU - Shu, Xiao Ou
AU - Long, Jirong
AU - Cai, Qiuyin
AU - Qi, Lu
AU - Xiang, Yong Bing
AU - Cho, Yoon Shin
AU - Tai, E. Shyong
AU - Li, Xiangyang
AU - Lin, Xu
AU - Chow, Wong Ho
AU - Go, Min Jin
AU - Seielstad, Mark
AU - Bao, Wei
AU - Li, Huaixing
AU - Cornelis, Marilyn C.
AU - Yu, Kai
AU - Wen, Wanqing
AU - Shi, Jiajun
AU - Han, Bok Ghee
AU - Sim, Xue Ling
AU - Liu, Liegang
AU - Qi, Qibin
AU - Kim, Hyung Lae
AU - Ng, Daniel P.K.
AU - Lee, Jong Young
AU - Kim, Young Jin
AU - Li, Chun
AU - Gao, Yu Tang
AU - Zheng, Wei
AU - Hu, Frank B.
PY - 2010/9
Y1 - 2010/9
N2 - 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 (r2<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.
AB - 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 (r2<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.
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U2 - 10.1371/journal.pgen.1001127
DO - 10.1371/journal.pgen.1001127
M3 - Article
C2 - 20862305
AN - SCOPUS:78049438674
SN - 1553-7390
VL - 6
JO - PLoS genetics
JF - PLoS genetics
IS - 9
M1 - e1001127
ER -
