Abstract
The risk of type 2 diabetes is approximately 2-fold higher in African Americans than in European Americans even after adjusting for known environmental risk factors, including socioeconomic status (SES), suggesting that genetic factors may explain some of this population difference in disease risk. However, relatively few genetic studies have examined this hypothesis in a large sample of African Americans with and without diabetes. Therefore, we performed an admixture analysis using 2,189 ancestry-informative markers in 7,021 African Americans (2,373 with type 2 diabetes and 4,648 without) from the Atherosclerosis Risk in Communities Study, the Jackson Heart Study, and the Multiethnic Cohort to 1) determine the association of type 2 diabetes and its related quantitative traits with African ancestry controlling for measures of SES and 2) identify genetic loci for type 2 diabetes through a genome-wide admixture mapping scan. The median percentage of African ancestry of diabetic participants was slightly greater than that of non-diabetic participants (study-adjusted difference = 1.6%, P<0.001). The odds ratio for diabetes comparing participants in the highest vs. lowest tertile of African ancestry was 1.33 (95% confidence interval 1.13–1.55), after adjustment for age, sex, study, body mass index (BMI), and SES. Admixture scans identified two potential loci for diabetes at 12p13.31 (LOD = 4.0) and 13q14.3 (Z score = 4.5, P = 6.6×10−6). In conclusion, genetic ancestry has a significant association with type 2 diabetes above and beyond its association with non-genetic risk factors for type 2 diabetes in African Americans, but no single gene with a major effect is sufficient to explain a large portion of the observed population difference in risk of diabetes. There undoubtedly is a complex interplay among specific genetic loci and non-genetic factors, which may both be associated with overall admixture, leading to the observed ethnic differences in diabetes risk.
Highlights
13% of the U.S adults have type 2 diabetes [1], representing a significant burden on public health in the United States
We have conducted a large-scale admixture genetic analysis in more than 7,000 African Americans to determine the association of African ancestry with type 2 diabetes and to map susceptibility loci for type 2 diabetes
With 2,373 cases with type 2 diabetes and 4,648 controls, we found that greater African ancestry was significantly associated with type 2 diabetes and hemoglobin A1c (HbA1c) values even after adjustment for body mass index (BMI) and markers of socioeconomic status (SES), including education, income, and occupation
Summary
13% of the U.S adults have type 2 diabetes [1], representing a significant burden on public health in the United States. Data from the National Health and Nutrition Examination Survey (NHANES) confirm the substantial racial disparity in diabetes across the U.S [1,3]. In the Atherosclerosis Risk in Communities (ARIC) Study, African Americans are twice as likely as whites to develop incident type 2 diabetes—a disparity which persists even after extensive adjustment for socioeconomic status (SES) and behavioral risk factors [4]. This persistent disparity suggests that genetic factors may contribute to ethnic differences in susceptibility to type 2 diabetes
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