From the Department of Biobehavioral Health, College of Health and Human Development, Pennsylvania State University, University Park (L.F.-R.).
Department of Epidemiology, Gillings School of Global Public Health (K.L.Y, H.M.H., C.A., S.-A.M.L., M.G., K.D., K.E.N.), University of North Carolina at Chapel Hill.
Circ Res. 2020 Jun 5;126(12):1816-1840. doi: 10.1161/CIRCRESAHA.120.315893. Epub 2020 Jun 4.
Genome-wide association studies have revolutionized our understanding of the genetic underpinnings of cardiometabolic disease. Yet, the inadequate representation of individuals of diverse ancestral backgrounds in these studies may undercut their ultimate potential for both public health and precision medicine. The goal of this review is to describe the imperativeness of studying the populations who are most affected by cardiometabolic disease, to the aim of better understanding the genetic underpinnings of the disease. We support this premise by describing the current variation in the global burden of cardiometabolic disease and emphasize the importance of building a globally and ancestrally representative genetics evidence base for the identification of population-specific variants, fine-mapping, and polygenic risk score estimation. We discuss the important ethical, legal, and social implications of increasing ancestral diversity in genetic studies of cardiometabolic disease and the challenges that arise from the (1) lack of diversity in current reference populations and available analytic samples and the (2) unequal generation of health-associated genomic data and their prediction accuracies. Despite these challenges, we conclude that additional, unprecedented opportunities lie ahead for public health genomics and the realization of precision medicine, provided that the gap in diversity can be systematically addressed. Achieving this goal will require concerted efforts by social, academic, professional and regulatory stakeholders and communities, and these efforts must be based on principles of equity and social justice.
全基因组关联研究极大地改变了我们对心血管代谢疾病遗传基础的理解。然而，这些研究中不同祖先背景的个体代表性不足，可能会削弱它们在公共卫生和精准医学方面的最终潜力。本综述的目的是描述研究受心血管代谢疾病影响最大的人群的必要性，旨在更好地了解疾病的遗传基础。我们通过描述当前全球心血管代谢疾病负担的变化来支持这一前提，并强调建立一个具有全球和祖先代表性的遗传证据基础的重要性，以确定特定人群的变异、精细映射和多基因风险评分估计。我们讨论了在心血管代谢疾病的遗传研究中增加祖先多样性所带来的重要伦理、法律和社会影响，以及当前参考人群和可用分析样本中存在的（1）多样性不足以及（2）健康相关基因组数据的生成不平等及其预测准确性等问题所带来的挑战。尽管存在这些挑战，但我们的结论是，只要能够系统地解决多样性差距问题，公共卫生基因组学和精准医学就将迎来前所未有的机遇。要实现这一目标，需要社会、学术、专业和监管利益相关者以及社区的共同努力，这些努力必须基于公平和社会正义原则。
