Few genome-wide association studies (GWAS) of type 2 diabetes (T2D) have been conducted in US Hispanics/Latinos of diverse backgrounds who are disproportionately affected by diabetes. We conducted a GWAS in 2499 T2D cases and 5247 controls from 6 Hispanic/Latino background groups in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Our GWAS identified two known loci (TCF7L2 and KCNQ1) reaching genome-wide significance level. Conditional analysis on known index SNPs indicated an additional independent signal at KCNQ1, represented by an African ancestry-specific variant, rs1049549 (OR=1.49 [95% CI 1.27, 1.75]). This association was consistent across Hispanic/Latino background groups and replicated in the Meta-analysis of type 2 DIabetes in African Americans Consortium. Among 80 previously known index SNPs at T2D loci, 66 SNPs showed consistency with the reported direction of associations and 14 SNPs significantly generalized to the HCHS/SOL. A genetic risk score based on these 80 index SNPs was significantly associated with T2D (OR=1.07 [1.06, 1.09] per risk allele), with a stronger effect observed in non-obese than obese individuals. Our study identified a novel independent signal suggesting an African ancestry-specific allele at KCNQ1 for T2D. Associations between previously identified loci and T2D were generally shown in a large cohort of US Hispanics/Latinos.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db16-1150/-/DC1.
- Received September 19, 2016.
- Accepted February 23, 2017.
- © 2017 by the American Diabetes Association.