Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
Hum Mol Genet. 2011 Jun 1;20(11):2273-84. doi: 10.1093/hmg/ddr092. Epub 2011 Mar 4.
The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10(-8)) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10(-8)). The top IBC association for SBP was rs2012318 (P= 6.4 × 10(-6)) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10(-6)) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity.
非裔美国人（AA）的高血压患病率高于其他美国人群；然而，很少有研究在 AA 中进行全基因组关联研究（GWAS）。在欧洲血统的人群中，GWAS 已经确定了 13 个与血压相关的基因变异位点。目前尚不清楚这些变异是否会使非洲血统的人群易患高血压。在这里，我们使用由 8591 名 AA 组成的候选基因关联资源（CARe）联盟，检查了与收缩压（SBP）和舒张压（DBP）相关的全基因组和候选基因关联。基因型包括利用 Affymetrix 6.0 阵列进行全基因组单核苷酸多态性（SNP）数据，利用 250 万 HapMap SNP 进行导入，并利用 50K 心血管基因中心阵列（ITMAT-Broad-CARe [IBC] 阵列）进行候选基因 SNP 数据。对于 Affymetrix 数据，DBP 最强的信号是位于 GPR98 和 ARRDC3 附近的 rs10474346（P=3.6×10(-8)）。对于 SBP，最强的信号是 C21orf91 中的 rs2258119（P=4.7×10(-8)）。SBP 的 IBC 最强关联是 rs2012318（P=6.4×10(-6)），位于 SLC25A42 附近，DBP 的最强关联是 rs2523586（P=1.3×10(-6)），位于 HLA-B 附近。在另外的 AA（n=11882）或欧洲裔美国人（n=69899）队列中，没有一个顶级变体得到复制。我们在 AA 样本中复制了先前报道的欧洲裔美国人血压 SNP（SH2B3，P=0.009；TBX3-TBX5，P=0.03；CSK-ULK3，P=0.0004）。这些遗传位点代表了迄今为止 AA 中 SBP 和 DBP 遗传影响的最佳证据。更广泛地说，这项工作支持这样一种观点，即 AA 的血压是一种具有遗传基础但也具有显著复杂性的特征。
