Genetics of Type 2 Diabetes in U.S. Hispanic/Latino Individuals: Results From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Diabetes. 2017 May;66(5):1419-1425. doi: 10.2337/db16-1150. Epub 2017 Mar 2.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • African Americans / genetics*
  • Aged
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Genotyping Techniques
  • Haplotypes
  • Hispanic Americans / genetics*
  • Humans
  • KCNQ1 Potassium Channel / genetics*
  • Linear Models
  • Male
  • Middle Aged
  • Obesity / complications
  • Polymorphism, Single Nucleotide
  • Risk Assessment
  • Transcription Factor 7-Like 2 Protein / genetics*
  • United States
  • Young Adult

Substances

  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human
  • TCF7L2 protein, human
  • Transcription Factor 7-Like 2 Protein