Singh Surina, Choudhury Ananyo, Hazelhurst Scott, Crowther Nigel, Boua Palwende, Sorgho Hermann, Agongo Godfred, Nonterah Engelbert, Micklesfield Lisa, Norris Shane, Kisiangani Isaac, Mohamed Shukri, Gomez-Olive Francesc, Tollman Stephen, Choma Solomon, Brandenburg Jean-Tristan, Ramsay Michele
Sydney Brenner Institute for Molecular Bioscience (SBIMB), University of the Witwatersrand.
University of the Witwatersrand.
Res Sq. 2023 Feb 13:rs.3.rs-2532794. doi: 10.21203/rs.3.rs-2532794/v1.
Most hypertension-related genome-wide association studies (GWAS) 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-related traits (systolic and diastolic blood pressure, pulse pressure, mean-arterial pressure and hypertension) from three sub-Saharan African geographic regions (N=10,775), identified two genome-wide significant signals (p<5E-08): systolic blood pressure near P2RY1 (rs77846204; intergenic variant, p=4.25E-08) and pulse pressure near Linc01256 (rs80141533; intergenic variant, p=4.25E-08). No genome-wide signals were detected for the AWI-Gen GWAS meta-analysis with previous African-ancestry GWASs (UK Biobank (African), Uganda Genome Resource). Suggestive signals (p<5E-06) were observed for all traits, with 29 displaying pleiotropic effects and several replicating known associations. Polygenic risk scores developed from studies on different ancestries had limited transferability, with multi-ancestry models providing better prediction. This study provides insights into the genetics and physiology of blood pressure variation in African populations.
尽管高血压(心血管疾病的主要风险因素)在非洲非常普遍,但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上。AWI-Gen研究对来自撒哈拉以南非洲三个地理区域(N = 10775)的血压相关性状(收缩压和舒张压、脉压、平均动脉压和高血压)进行了GWAS荟萃分析,确定了两个全基因组显著信号(p<5E-08):P2RY1附近的收缩压(rs77846204;基因间变异,p = 4.25E-08)和Linc01256附近的脉压(rs80141533;基因间变异,p = 4.25E-08)。在AWI-Gen GWAS荟萃分析与之前的非洲血统GWAS(英国生物银行(非洲)、乌干达基因组资源)中未检测到全基因组信号。所有性状均观察到提示性信号(p<5E-06),其中29个显示出多效性效应,还有几个重复了已知的关联。基于不同血统研究开发的多基因风险评分的可转移性有限,多血统模型提供了更好的预测。这项研究为非洲人群血压变异的遗传学和生理学提供了见解。