Kessler Thorsten, Schunkert Heribert
German Heart Centre Munich, Department of Cardiology, Technical University of Munich, Munich, Germany.
German Centre for Cardiovascular Research (DZHK e.V.), partner site Munich Heart Alliance, Munich, Germany.
JACC Basic Transl Sci. 2021 Jul 26;6(7):610-623. doi: 10.1016/j.jacbts.2021.04.001. eCollection 2021 Jul.
Many cardiovascular diseases are facilitated by strong inheritance. For example, large-scale genetic studies identified hundreds of genomic loci that affect the risk of coronary artery disease. At each of these loci, common variants are associated with disease risk with robust statistical evidence but individually small effect sizes. Only a minority of candidate genes found at these loci are involved in the pathophysiology of traditional risk factors, but experimental research is making progress in identifying novel, and, in part, unexpected mechanisms. Targets identified by genome-wide association studies have already led to the development of novel treatments, specifically in lipid metabolism. This review summarizes recent genetic and experimental findings in this field. In addition, the development and possible clinical usefulness of polygenic risk scores in risk prediction and individualization of treatment, particularly in lipid metabolism, are discussed.
许多心血管疾病受强大的遗传因素影响。例如,大规模基因研究确定了数百个影响冠状动脉疾病风险的基因组位点。在这些位点中的每一个,常见变异与疾病风险相关,有强有力的统计证据,但个体效应大小较小。在这些位点发现的候选基因中,只有少数参与传统危险因素的病理生理学,但实验研究在确定新的、部分意想不到的机制方面正在取得进展。全基因组关联研究确定的靶点已导致新疗法的开发,特别是在脂质代谢方面。本综述总结了该领域最近的遗传和实验发现。此外,还讨论了多基因风险评分在风险预测和治疗个体化,特别是在脂质代谢方面的发展及其可能的临床应用价值。