Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Division of Human Genetics, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Nat Commun. 2023 Dec 16;14(1):8376. doi: 10.1038/s41467-023-44079-0.
Most hypertension-related genome-wide association studies (GWASs) focus on non-African populations, despite hypertension (a major risk factor for cardiovascular disease) being highly prevalent in Africa. The AWI-Gen study GWAS meta-analysis for blood pressure (BP)-related traits (systolic and diastolic BP, pulse pressure, mean-arterial pressure and hypertension) from three sub-Saharan African geographic regions (N = 10,775), identifies two novel genome-wide significant signals (p < 5E-08): systolic BP near P2RY1 (rs77846204; intergenic variant, p = 4.95E-08) and pulse pressure near LINC01256 (rs80141533; intergenic variant, p = 1.76E-08). No genome-wide signals are detected for the AWI-Gen GWAS meta-analysis with previous African-ancestry GWASs (UK Biobank (African), Uganda Genome Resource). Suggestive signals (p < 5E-06) are observed for all traits, with 29 SNPs associating with more than one trait and several replicating known associations. Polygenic risk scores (PRSs) developed from studies on different ancestries have limited transferability, with multi-ancestry PRS providing better prediction. This study provides insights into the genetics of BP variation in African populations.
大多数与高血压相关的全基因组关联研究(GWAS)都集中在非非洲人群中,尽管高血压(心血管疾病的主要危险因素)在非洲非常普遍。来自撒哈拉以南非洲三个地理区域的 AWI-Gen 研究 GWAS 对与血压(收缩压和舒张压、脉压、平均动脉压和高血压)相关的特征进行了荟萃分析(N=10775),确定了两个新的全基因组显著信号(p<5E-08):收缩压附近的 P2RY1(rs77846204;基因间变异,p=4.95E-08)和脉压附近的 LINC01256(rs80141533;基因间变异,p=1.76E-08)。与以前的非洲裔 GWAS(英国生物库(非洲)、乌干达基因组资源)的 AWI-Gen GWAS 荟萃分析没有检测到全基因组信号。所有特征都观察到提示性信号(p<5E-06),29 个 SNP 与一个以上特征相关,并且有几个特征复制了已知的关联。来自不同祖先的研究中开发的多基因风险评分(PRS)的可转移性有限,多祖先 PRS 提供了更好的预测。本研究为非洲人群的血压变异遗传学提供了新的见解。