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, Xiangyang Li, Xu Lin, Wong Ho Chow, Min Jin Go, Mark Seielstad, Wei Bao, Huaixing Li, Marilyn C. Cornelis, Kai Yu, Wanqing Wen, Jiajun Shi, Bok Ghee Han, Xue Ling SimLiegang Liu, Qibin Qi, Hyung Lae Kim, Daniel P.K. Ng, Jong Young Lee, Young Jin Kim, Chun Li, Yu Tang Gao, Wei Zheng, Frank B. Hu

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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 (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.

Original languageEnglish (US)
Article numbere1001127
JournalPLoS genetics
Volume6
Issue number9
DOIs
StatePublished - Sep 1 2010
Externally publishedYes

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ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Shu, X. O., Long, J., Cai, Q., Qi, L., Xiang, Y. B., Cho, Y. S., Tai, E. S., Li, X., Lin, X., Chow, W. H., Go, M. J., Seielstad, M., Bao, W., Li, H., Cornelis, M. C., Yu, K., Wen, W., Shi, J., Han, B. G., ... Hu, F. B. (2010). Identification of new genetic risk variants for Type 2 Diabetes. PLoS genetics, 6(9), [e1001127]. https://doi.org/10.1371/journal.pgen.1001127