A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, 70211, Finland; Department of Pathology and Laboratory Medicine, University of California, UCLA, Los Angeles, USA.
A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, 70211, Finland.
Atherosclerosis. 2023 Jun;374:87-98. doi: 10.1016/j.atherosclerosis.2023.01.019. Epub 2023 Feb 2.
Genome-wide Association Studies (GWAS) have identified more than 300 loci associated with coronary artery disease (CAD), defining the genetic risk map of the disease. However, the translation of the association signals into biological-pathophysiological mechanisms constitute a major challenge. Through a group of examples of studies focused on CAD, we discuss the rationale, basic principles and outcomes of the main methodologies implemented to prioritize and characterize causal variants and their target genes. Additionally, we highlight the strategies as well as the current methods that integrate association and functional genomics data to dissect the cellular specificity underlying the complexity of disease mechanisms. Despite the limitations of existing approaches, the increasing knowledge generated through functional studies helps interpret GWAS maps and opens novel avenues for the clinical usability of association data.
全基因组关联研究 (GWAS) 已经确定了 300 多个与冠状动脉疾病 (CAD) 相关的基因座，定义了该疾病的遗传风险图谱。然而，将关联信号转化为生物病理生理学机制是一个重大挑战。通过一组专注于 CAD 的研究示例，我们讨论了主要方法学的基本原理、基本原则和结果，这些方法学被用于优先考虑和描述因果变异及其靶基因。此外，我们还强调了整合关联和功能基因组学数据以剖析疾病机制复杂性背后的细胞特异性的策略和当前方法。尽管现有方法存在局限性，但通过功能研究产生的日益增加的知识有助于解释 GWAS 图谱，并为关联数据的临床应用开辟新途径。
