The African Computational Genomics (TACG) Research Group, MRC/UVRI and LSHTM, Entebbe 7545, Uganda.
The African Center of Excellence in Bioinformatics of Bamako (ACE-B), University of Sciences, Techniques and Technologies of Bamako, Bamako 3206, Mali.
Int J Mol Sci. 2023 Jan 21;24(3):2164. doi: 10.3390/ijms24032164.
High blood pressure (HBP) has been implicated as a major risk factor for cardiovascular diseases in several populations, including individuals of African ancestry. Despite the elevated burden of HBP-induced cardiovascular diseases in Africa and other populations of African descent, limited genetic studies have been carried out to explore the genetic mechanism driving this phenomenon. We performed genome-wide association univariate and multivariate analyses of both systolic (SBP) and diastolic blood pressure (DBP) traits in 80,950 individuals of African ancestry. We used summary statistics data from six independent cohorts, including the African Partnership for Chronic Disease Research (APCDR), the UK Biobank, and the Million Veteran Program (MVP). FUMA was used to annotate, prioritize, visualize, and interpret our findings to gain a better understanding of the molecular mechanism(s) underlying the genetics of BP traits. Finally, we undertook a Bayesian fine-mapping analysis to identify potential causal variants. Our meta-analysis identified 10 independent variants associated with SBP and 9 with DBP traits. Whilst our multivariate GWAS method identified 21 independent signals, 18 of these SNPs have been previously identified. SBP was linked to gene sets involved in biological processes such as synapse assembly and cell-cell adhesion via plasma membrane adhesion. Of the 19 independent SNPs identified in the BP meta-analysis, only 11 variants had posterior probability (PP) of > 50%, including one novel variant: rs562545 (, PP = 77%). To facilitate further research and fine-mapping of high-risk loci/variants in highly susceptible groups for cardiovascular disease and other related traits, large-scale genomic datasets are needed. Our findings highlight the importance of including ancestrally diverse populations in large GWASs and the need for diversity in genetic research.
高血压（HBP）已被证实为多个人群（包括非洲裔人群）心血管疾病的主要危险因素。尽管高血压引起的心血管疾病在非洲和其他非洲裔人群中负担沉重，但针对驱动这一现象的遗传机制的研究非常有限。我们对 80950 名非洲裔个体的收缩压（SBP）和舒张压（DBP）特征进行了全基因组关联单变量和多变量分析。我们使用了六个独立队列（包括非洲慢性病合作研究伙伴关系、英国生物银行和百万老兵计划）的汇总统计数据。FUMA 被用于注释、优先级排序、可视化和解释我们的发现，以更好地了解 BP 特征遗传背后的分子机制。最后，我们进行了贝叶斯精细映射分析，以识别潜在的因果变异。我们的荟萃分析确定了 10 个与 SBP 相关的独立变异和 9 个与 DBP 特征相关的独立变异。虽然我们的多变量 GWAS 方法确定了 21 个独立信号，但其中 18 个 SNP 以前已经被确定。SBP 与涉及生物过程的基因集相关，例如突触组装和细胞膜粘附的细胞-细胞粘附。在 BP 荟萃分析中确定的 19 个独立 SNP 中，只有 11 个变体具有> 50%的后验概率（PP），包括一个新变体：rs562545（，PP = 77%）。为了促进对心血管疾病和其他相关特征的高风险基因座/变体的进一步研究和精细映射，需要大规模的基因组数据集。我们的研究结果强调了在大型 GWAS 中纳入具有不同遗传背景的人群的重要性，以及在遗传研究中需要多样性。
