title: African ancestry and its correlation to type 2 diabetes in African Americans: a genetic admixture analysis in three U.S. population cohorts.
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.
authors.affiliation: Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Cheng
authors.forename: David
authors.initials: D
authors.lastname: Reich
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.forename: Arti
authors.initials: A
authors.lastname: Tandon
authors.forename: Nick
authors.initials: N
authors.lastname: Patterson
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Selvin
authors.forename: Selvin
authors.initials: S
authors.lastname: Elizabeth
authors.forename: Ermeg L
authors.initials: EL
authors.lastname: Akylbekova
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Brancati
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: David
authors.initials: D
authors.lastname: Altshuler
authors.forename: Herman A
authors.initials: HA
authors.lastname: Taylor
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
authors.forename: James G
authors.initials: JG
authors.lastname: Wilson
authors.forename: W H Linda
authors.initials: WH
authors.lastname: Kao
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000818:Animals; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011446:Prospective Studies; D019655:Quantitative Trait, Heritable; D012307:Risk Factors; D014481:United States; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D005819:Genetic Markers