Singh S, Brandenburg J-T, Choudhury A, Gómez-Olivé F X, Ramsay M
Sydney Brenner Institute for Molecular Bioscience (SBIMB), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Division of Human Genetics, School of Pathology, National Health Laboratory Service and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Front Genet. 2021 Oct 20;12:699445. doi: 10.3389/fgene.2021.699445. eCollection 2021.
Despite hypertension being highly prevalent in individuals with African-ancestry, they are under-represented in large genome-wide association studies. Inclusion of African participants is essential to better understand genetic associations with blood pressure-related traits in Africans. This systematic review critically evaluates existing studies with African-ancestry participants and identifies knowledge gaps. We followed the PRISMA protocol, HuGE Review handbook to identify literature on original research, in English, on genetic association studies for blood pressure-related traits (systolic and diastolic blood pressure, pulse and mean-arterial pressure, and hypertension) in populations with African-ancestry (January 2007 to April 2020). A narrative synthesis of the evidence was conducted. Twelve studies with African-ancestry participants met the eligibility criteria, within which 10 studies met the additional genetic association data criteria (i.e., reporting only on African-ancestry participants). Across the five blood pressure-related traits, 26 genome-wide significantly associated SNPs were identified, with six SNPs linked to more than one trait, illustrating pleiotropic effects. Among the SNP associations, 12 had not previously been described in non-African studies. The limited number of relevant studies highlights the dearth of genomic association studies on participants with African-ancestry, especially those located within Africa. Variations in study methodology, participant inclusion, adjustment for covariates (e.g., antihypertensive medication) and relatively small sample sizes make comparisons challenging, and have resulted in fewer significant associations, compared to large European studies. Regional variation in the prevalence and associated risk factors of hypertension across Africa makes a compelling argument to develop African cohorts to facilitate large genomic studies, using African-centric arrays. Data harmonisation and comparable study designs, such as described in the H3Africa CHAIR initiative, provide a good example toward achieving this goal. SS and J-TB were funded by the South African National Research Foundation. MR is a South African Research Chair in Genomics and Bioinformatics of African populations hosted by the University of the Witwatersrand, funded by the Department of Science and Innovation, and administered by the NRF. This review was registered at PROSPERO (registration number: CRD42020179221) and OSF (registration DOI: 10.17605/OSF.IO/QT2HA).
尽管高血压在非洲裔人群中极为普遍，但在大规模全基因组关联研究中，他们的代表性不足。纳入非洲参与者对于更好地理解非洲人与血压相关性状的遗传关联至关重要。本系统综述对现有涉及非洲裔参与者的研究进行了批判性评估，并确定了知识空白。我们遵循PRISMA协议、HuGE综述手册，以识别2007年1月至2020年4月期间关于非洲裔人群中血压相关性状（收缩压和舒张压、脉搏和平均动脉压以及高血压）的遗传关联研究的英文原创研究文献。对证据进行了叙述性综合分析。12项涉及非洲裔参与者的研究符合纳入标准，其中10项研究符合额外的遗传关联数据标准（即仅报告非洲裔参与者）。在五个与血压相关的性状中，共鉴定出26个全基因组显著相关的单核苷酸多态性（SNP），其中六个SNP与多个性状相关，显示出多效性效应。在这些SNP关联中，有12个此前在非非洲研究中未被描述。相关研究数量有限凸显了针对非洲裔参与者，尤其是非洲境内参与者的基因组关联研究的匮乏。研究方法、参与者纳入标准、协变量调整（如抗高血压药物）的差异以及相对较小的样本量使得比较具有挑战性，与大型欧洲研究相比，显著关联较少。非洲各地高血压患病率和相关危险因素的区域差异有力地证明了有必要利用以非洲为中心的阵列开发非洲队列，以促进大型基因组研究。数据协调和可比的研究设计，如H3Africa CHAIR倡议中所描述的，为实现这一目标提供了一个很好的范例。SS和J-TB由南非国家研究基金会资助。MR是由威特沃特斯兰德大学主办的非洲人群基因组学和生物信息学南非研究主席，由科学与创新部资助，由NRF管理。本综述已在PROSPERO（注册号：CRD42020179221）和OSF（注册DOI：10.17605/OSF.IO/QT2HA）注册。
