William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
Cells. 2023 Sep 8;12(18):2232. doi: 10.3390/cells12182232.
Genome-wide association studies (GWAS) have identified a large number of genetic loci for coronary artery disease (CAD), with many located close to genes associated with traditional CAD risk pathways, such as lipid metabolism and inflammation. It is becoming evident with recent CAD GWAS meta-analyses that vascular pathways are also highly enriched and present an opportunity for novel therapeutics. This review examines GWAS-enriched vascular gene loci, the pathways involved and their potential role in CAD pathogenesis. The functionality of variants is explored from expression quantitative trait loci, massively parallel reporter assays and CRISPR-based gene-editing tools. We discuss how this research may lead to novel therapeutic tools to treat cardiovascular disorders.
全基因组关联研究（GWAS）已经确定了大量与冠状动脉疾病（CAD）相关的遗传位点，其中许多位于与传统 CAD 风险途径相关的基因附近，如脂质代谢和炎症。最近的 CAD GWAS 荟萃分析表明，血管途径也高度富集，为新型治疗方法提供了机会。这篇综述检查了 GWAS 富集的血管基因位点、涉及的途径及其在 CAD 发病机制中的潜在作用。通过表达数量性状基因座、大规模平行报告基因检测和基于 CRISPR 的基因编辑工具来探索变体的功能。我们讨论了这项研究如何为治疗心血管疾病的新型治疗工具提供思路。
