A High-Density Admixture Scan in 1,670 African Americans with Hypertension

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Abstract
Hypertension (HTN) is a devastating disease with a higher incidence in African Americans than European Americans, inspiring searches for genetic variants that contribute to this difference. We report the results of a large-scale admixture scan for genes contributing HTN risk, in which we screened 1,670 African Americans with HTN and 387 control individuals for regions of the genome with elevated proportion of African or European ancestry. No loci were identified that were significantly associated with HTN. We also searched for evidence of an admixture signal at 40 candidate genes and eight previously reported linkage peaks, but none appears to contribute substantially to the differential HTN risk between African and European Americans. Finally, we observed nominal association at one of the loci detected in the admixture scan of Zhu et al. 2005 (p = 0.016 at 6q24.3 correcting for four hypotheses tested), although we caution that the significance is marginal and the estimated odds ratio of 1.19 per African allele is less than what would be expected from the original report; thus, further work is needed to follow up this locus. High blood pressure is more frequent and severe among African Americans than European Americans. To explore whether there are genetic underpinnings to this pattern, we screened the genomes of 1,670 African Americans, searching for loci at which people with hypertension (HTN) have more than the average proportion of African ancestry (eighty percent). We do not detect any region of clearly significant association. In a previous, smaller admixture scan for HTN genes, Zhu and colleagues (2005) reported two regions of association, which we would have expected to replicate if they were as strong as they initially appeared. While we detect marginal evidence of association at one, the signal is very weak, and much weaker than would have been expected from the previous report, so further work is necessary to understand this region. Our results are consistent with there being no common variants with a strong effect accounting for differences in HTN prevalence between African and European Americans. This increases the weight of evidence that non-genetic causes explain most of the difference in rates across populations.