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Am J Hum Genet ; 93(3): 545-54, 2013 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-23972371

RESUMO

High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0 × 10(-8)) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability.


Assuntos
População Negra/genética , Pressão Sanguínea/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Característica Quantitativa Herdável , África , Estudos de Coortes , Bases de Dados Genéticas , Loci Gênicos/genética , Humanos , Polimorfismo de Nucleotídeo Único/genética , Reprodutibilidade dos Testes
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