Abstract 15011: African Admixture is Associated With Subcortical White Matter Hyperintensities in African Americans With a Family History of Early Onset Coronary Disease
Background: African Americans have a higher risk of stroke and related morbidity and mortality than do European Americans. Deep white matter hyperintensities (WMH) in the subcortical region of the brain on magnetic resonance imaging (MRI) are thought to represent ischemic small vessel disease and have been associated with stroke. Moreover, the burden of WMH is higher in African American populations compared to Americans of European ancestry. Because African Americans are a heterogeneous population with significant racial admixture, we investigated the degree to which global African Ancestry was associated with WMH in a self-identified African American population from families with early-onset CAD.
Methods: We screened 277 African Americans for traditional cardiovascular risk factors and for subcortical WMH using a 3-Tesla cranial MRI. WMH volume was measured using automated software and extreme WMH volume was defined as the upper quartile. All participants had genomewide genotyping performed using the Illumina 1Mv1 C Human array. Using a panel of approximately 18,000 ancestry informative markers sub-selected from the genomewide array, global fraction of African, European and Asian ancestry of each sample was determined using STRUCTURE and ancestral HapMap reference populations from Yoruba, Utah, and Asia.
Results: Participants were 51.3 ± 10.9 years of age (range 29 to 74) and 64% female. Average African ancestry was 79.1% ± 10.0 (range 46.7 to 97.6). Multivariate GEE regression analysis showed that African ancestry was significantly associated with volume of WMH (p=0.01), adjusting for age, sex, current smoking behavior and the presence of diabetes, hypertension, and obesity. There was a 2.6 greater odds (95% CI: 1.3 to 5.2) of having extreme WMH volume if African ancestry was ≥86.1% (upper quartile) compared to African ancestry <86.1%, also independent of age, sex, and risk factors.
Conclusion: African ancestry is associated with a higher burden of WMH in African Americans, independent of age, sex and other influential variables. We are extending this investigation to local admixture mapping analysis to find specific loci that may help to explain small vessel disease of the brain.
- © 2013 by American Heart Association, Inc.