ADMIXTURE MAPPING IDENTIFIES ASSOCIATION OF THE VNN1 GENE WITH HYPERTENSION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Migration patterns in modern societies have created the opportunity to use population admixture as a strategy to identify susceptibility genes. To implement this strategy, we genotyped a highly informative ancestry marker panel of 2270 single nucleotide polymorphisms in a random population sample of African Americans (N = 1743), European Americans (N = 1000) and Mexican Americans (N = 581). We then examined the evidence for over-transmission of specific loci to cases from one of the two ancestral populations. Hypertension cases and controls were defined based on standard clinical criteria. Both case-only and case-control analyses were performed among African Americans. With the genome-wide markers we replicated the findings identified in our previous admixture mapping study on chromosomes 6 and 21. For case-control analysis, we then genotyped 51 missense SNPs in 36 genes spaced across an 18.3 Mb region. Further analyses demonstrated that the missense SNP rs2272996 (or N131S) in the VNN1 gene was significantly associated with hypertension in African Americans and the association was replicated in Mexican Americans; a non-significant opposite association was observed in European Americans. This SNP also accounted for most of the evidence observed in the admixture analysis on chromosome 6. Despite these encouraging results, susceptibility loci for hypertension have been exceptionally difficult to localize and confirmation by independent studies will be necessary to establish these findings.