Genetics of type 2 diabetes in U.S. Hispanic/Latino individuals: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Qibin Qi, Adrienne M. Stilp, Tamar Sofer, Jee Young Moon, Bertha Hidalgo, Adam A. Szpiro, Tao Wang, Maggie C.Y. Ng, Xiuqing Guo, Yii Der Ida Chen, Kent D. Taylor, M. Larissa Aviles-Santa, George Papanicolaou, James S. Pankow, Neil Schneiderman, Cathy C. Laurie, Jerome I. Rotter, Robert C. Kaplan

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Few genome-wide association studies (GWAS) of type 2 diabetes (T2D) have been conducted in U.S. Hispanics/Latinos of diverse backgrounds who are disproportionately affected by diabetes. We conducted a GWAS in 2,499 T2D case subjects and 5,247 control subjects from six 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 levels. Conditional analysis on known index single nucleotide polymorphisms (SNPs) indicated an additional independent signal at KCNQ1, represented by an African ancestry-specific variant, rs1049549 (odds ratio 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 (MEDIA) 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 (odds ratio 1.07 [1.06-1.09] per risk allele), with a stronger effect observed in nonobese than in 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 U.S. Hispanics/Latinos.

Original languageEnglish (US)
Pages (from-to)1419-1425
Number of pages7
JournalDiabetes
Volume66
Issue number5
DOIs
StatePublished - May 1 2017

Bibliographical note

Publisher Copyright:
© 2017 by the American Diabetes Association.

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