Department of Epidemiology, University of North Carolina at Chapel Hill, NC 27599, USA.
Am J Hum Genet. 2013 Sep 5;93(3):545-54. doi: 10.1016/j.ajhg.2013.07.010. Epub 2013 Aug 22.
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.
高血压(BP)在非裔美国人中比任何其他美国族群更为普遍,且其心血管疾病(CVD)的表现更为严重。已经发表了几项小型的非裔血统(AA)BP 全基因组关联研究(GWAS),但迄今为止,其发现尚未得到复制。我们报告了一项大型 AA BP GWAS 元分析,该分析包括来自 19 个发现队列的 29,378 个人,随后在 AA(n = 10,386)、欧洲血统(EA)(n = 69,395)和东亚血统(n = 19,601)的其他样本中进行了复制。在跨种族元分析中,五个基因座(EVX1-HOXA、ULK4、RSPO3、PLEKHG1 和 SOX6)在经过多重检验校正后,达到了收缩压或舒张压的全基因组显著水平(p < 1.0×10(-8))。这些 BP 基因座中有三个(EVX1-HOXA、RSPO3 和 PLEKHG1)以前与 BP 无关。我们还在已知的 BP 基因座(SOX6)中确定了一个独立信号,并为另外四个经过验证的 BP 基因座提供了精细映射的证据。我们还证明,联合考虑的经过验证的 EA BP GWAS 基因座在 AA 样本中具有显著影响。因此,这些发现表明 BP 基因座可能在研究人群中具有普遍影响,证明多民族样本是识别、精细映射和理解其特征变异性的重要组成部分。