Saturday, November 17, 2007

Genetic influence on hypertension differences between African and European Americans

In this large scale admixture scan, they don't find evidence for an effect of genetic differences between Africans and Europeans on hypertension risk. They discuss the implications in that the incidence disparity between African Americans and European Americans may be due more to the effects of the environment, but they also discuss some of the limitations of their study.
Interestingly they look at the effects of loci that were proposed to have an effect in an earlier study:
We also examined five candidate genes that were highlighted by Young et al. [3], who proposed that HTN may arise from the interaction of salt-availability in humans populations with heat-adapted alleles that vary widely in frequency across populations. None of the five genes produced an admixture signal, suggesting that the underlying alleles do not explain a substantial amount of differential HTN risk across these populations.
This earlier study, also in PLoS Genetics, suggests that:
... the current epidemic of hypertension is due to exposures of the modern period interacting with ancestral susceptibility. Modern populations differ in susceptibility to these new exposures, however, such that those from hot environments are more susceptible to hypertension than populations from cold environments. This differential susceptibility is likely due to our history of adaptation to climate.
High-Density Admixture Scan in 1,670 African Americans with Hypertension

Rahul C. Deo, Nick Patterson, Arti Tandon, Gavin J. McDonald, Christopher A. Haiman, Kristin Ardlie, Brian E. Henderson, Sean O. Henderson, David Reich

PLoS Genetics 3(11): e196
Author Summary: 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.

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