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Lookup NU author(s): Professor Heather Cordell,
Professor Bernard Keavney
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OBJECTIVE To determine if 16 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2DM) in Europeans are also associated with T2DM in South Asians and Latinos and if they can add to the prediction of incident T2DM in a high-risk population.RESEARCH DESIGN AND METHODS In the EpiDREAM prospective cohort study, physical measures, questionnaires, and blood samples were collected from 25,063 individuals at risk for dysglycemia. Sixteen SNPs that have been robustly associated with T2DM in Europeans were genotyped. Among 15,466 European, South Asian, and Latino subjects, we examined the association of these 16 SNPs alone and combined in a gene score with incident cases of T2DM (n = 1,016) that developed during 3.3 years of follow-up.RESULTS Nine of the 16 SNPs were significantly associated with T2DM, and their direction of effect was consistent across the three ethnic groups. The gene score was significantly higher among subjects who developed incident T2DM (cases vs. noncases: 16.47 [2.50] vs. 15.99 [2.56]; P = 0.00001). The gene score remained an independent predictor of incident T2DM, with an odds ratio of 1.08 (95% CI 1.05-1.11) per additional risk allele after adjustment for T2DM risk factors. The gene score in those with no family history of T2DM was 16.02, whereas it was 16.19 in those with one parent with T2DM and it was 16.32 in those with two parents with T2DM (P trend = 0.0004). The C statistic of T2DM risk factors was 0.708 (0.691-0.725) and increased only marginally to 0.714 (0.698-0.731) with the addition of the gene score (P for C statistic change = 0.0052).CONCLUSIONS T2DM genetic associations are generally consistent across ethnic groups, and a gene score only adds marginal information to clinical factors for T2DM prediction.
Author(s): Anand SS, Meyre D, Pare G, Bailey SD, Xie CC, Zhang XH, Montpetit A, Desai D, Bosch J, Mohan V, Diaz R, McQueen MJ, Cordell HJ, Keavney B, Yusuf S, Gaudet D, Gerstein H, Engert JC, EpiDREAM Genetics Investigators
Publication type: Article
Publication status: Published
Journal: Diabetes Care
Print publication date: 19/04/2013
ISSN (print): 0149-5992
ISSN (electronic): 1935-5548
Publisher: American Diabetes Association
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