Admixture mapping of anthropometric traits in the Black Women's Health Study: evidence of a shared African ancestry component with birth weight and type 2 diabetes.

Abstract

Prevalence of obesity, type 2 diabetes (T2D), and being born with low birth weight are much higher in African American women compared to U.S. white women. Genetic factors may contribute to the excess risk of these conditions. We conducted admixture mapping of body mass index (BMI) at age 18, adult BMI, and adult waist circumference and waist-to-hip ratio adjusted for BMI using 2918 ancestral informative markers in 2596 participants of the Black Women's Health Study. We also searched for evidence of shared African genetic ancestry components among the four examined anthropometric traits and among birth weight and T2D. We found that global percent African ancestry was associated with higher adult BMI. We also found that African ancestry at 9q34 was associated with lower BMI at age 18. Our shared ancestry analysis identified ten genomic regions with local African ancestry associated with multiple traits. Seven out of these ten genomic loci were related to T2D risk. Of special interest is the 12q14-21 region where local African ancestry was associated with low birth weight, low BMI, high BMI-adjusted waist-to-hip ratio, and high T2D risk. Findings in the 12q14-21 genomic locus are consistent with the fetal insulin hypothesis that postulates that low birth weight and T2D have a common genetic basis, and they support the hypothesis of a shared African genetic ancestry component linking low birth weight and T2D in African Americans. Future studies should identify the actual genetic variants responsible for the clustering of these conditions in African Americans.