Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
The African Computational Genomics (TACG) Research Group, MRC/UVRI, and LSHTM, Entebbe, Uganda.
PLoS One. 2023 Nov 29;18(11):e0294341. doi: 10.1371/journal.pone.0294341. eCollection 2023.
Cardiovascular diseases are some of the leading causes of death worldwide, with coronary artery disease leading as one of the primary causes of mortality in both the developing and developed worlds. Despite its prevalence, there is a disproportionately small number of studies conducted in populations of non-European ancestry, with the limited sample sizes of such studies further restricting the power and generalizability of respective findings. This research aimed at understanding the differences in the genetic architecture of coronary artery disease (CAD) in populations of diverse ancestries in order to contribute towards the understanding of the pathophysiology of coronary artery disease.
We performed a systematic review on the 6th of October, 2022 summarizing genome-wide association studies on coronary artery disease, while employing the GWAS Catalog as an independent database to support the search. We developed a framework to assess the methodological quality of each study. We extracted and grouped associated single nucleotide polymorphisms and genes according to ancestry groups of participants.
We identified 3100 studies, of which, 36 relevant studies were included in this research. Three of the studies that were included were not listed in the GWAS Catalog, highlighting the value of conducting an independent search alongside established databases in order to ensure the full research landscape has been captured. 743,919 CAD case participants from 25 different countries were analysed, with 61% of the studies identified in this research conducted in populations of European ancestry. No studies investigated populations of Africans living in continental Africa or admixed American ancestry groups besides African-Americans, while limited sample sizes were included of population groups besides Europeans and East Asians. This observed disproportionate population representation highlights the gaps in the literature, which limits our ability to understand coronary artery disease as a global disease. 71 genetic loci were identified to be associated with coronary artery disease in more than one article, with ancestry-specific genetic loci identified in each respective population group which were not detected in studies of other ancestries.
Although the replication and validation of these variants are still warranted, these finding are indicative of the value of including diverse ancestry populations in GWAS reference panels, as a more comprehensive understanding of the genetic architecture and pathophysiology of CAD can be achieved.
心血管疾病是全球范围内一些主要的死亡原因，其中冠心病是发展中国家和发达国家主要的死亡原因之一。尽管它很普遍，但在非欧洲血统的人群中进行的研究数量相对较少，而且这些研究的样本量有限，进一步限制了各自研究结果的有效性和普遍性。这项研究旨在了解不同血统人群中冠心病遗传结构的差异，以便更好地了解冠心病的病理生理学。
我们于 2022 年 10 月 6 日进行了系统回顾，总结了冠心病的全基因组关联研究，同时使用 GWAS 目录作为独立数据库来支持搜索。我们开发了一个框架来评估每项研究的方法学质量。我们根据参与者的种族群体提取和分组相关的单核苷酸多态性和基因。
我们确定了 3100 项研究，其中 36 项相关研究纳入了本研究。纳入的三项研究并未在 GWAS 目录中列出，这突出了在进行独立搜索的同时结合使用已建立的数据库以确保全面捕获研究全貌的重要性。来自 25 个不同国家的 743919 名冠心病病例参与者进行了分析，其中 61%的研究是在欧洲血统人群中进行的。没有研究调查过生活在非洲大陆的非洲人或除非洲裔美国人以外的混合美洲血统群体，而除了欧洲人和东亚人以外的人群的样本量有限。这种观察到的不成比例的人群代表性突出了文献中的差距，这限制了我们将冠心病作为一种全球性疾病来理解的能力。在超过一篇文章中发现了 71 个与冠心病相关的遗传位点，在每个相应的人群群体中都发现了与其他血统研究中未检测到的遗传位点。
尽管这些变体的复制和验证仍然需要，但这些发现表明，在 GWAS 参考群体中纳入不同血统的人群具有重要价值，因为可以更全面地了解 CAD 的遗传结构和病理生理学。
