Polygenic Risk and Coronary Artery Disease Severity.

IF 6 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Circulation: Genomic and Precision Medicine Pub Date : 2024-10-01 Epub Date: 2024-08-08 DOI:10.1161/CIRCGEN.123.004470

Alborz Sherafati, Kristjan Norland, Mohammadreza Naderian, Daniel J Schaid, Iftikhar J Kullo

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引用次数: 0

Abstract

Background: Coronary atherosclerotic burden and adverse coronary heart disease events are related phenotypes with likely shared genetic cause.

Methods: We analyzed 6021 patients with available coronary angiography, genotyping, and exome sequencing data. We tested for associations of polygenic risk scores for coronary heart disease (PRS_CHD) with multiple measures of coronary artery disease (CAD) severity. We assessed the joint associations of PRS_CHD and pathogenic/likely pathogenic variants in 3 familial hypercholesterolemia genes, with CAD severity. We performed mediation analyses to explore whether CAD severity mediated the association of PRS_CHD with prevalent coronary heart disease and incident myocardial infarction.

Results: A 1-SD increase in PRS_CHD was associated with multiple measures of CAD severity, including the log Gensini score (β, 0.31 [95% CI, 0.28-0.33]). Carrying a pathogenic/likely pathogenic familial hypercholesterolemia variant was associated with a higher log Gensini score after adjustment for PRS_CHD (β, 0.21 [95% CI, 0.03-0.38]). A 1-SD increase in PRS_CHD was associated with incident myocardial infarction over a mean follow-up of 9.2 years (hazard ratio, 1.20 [95% CI, 1.13-1.27]; P=5×10^-¹⁰), and the Gensini score mediated 90% of this association.

Conclusions: PRS_CHD was associated with multiple measures of CAD severity. The association of PRS_CHD with incident myocardial infarction was almost fully mediated by CAD severity, indicating a considerable genetic overlap between the 2 phenotypes.

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多基因风险与冠心病严重程度

背景：冠状动脉粥样硬化负担和冠心病不良事件是相关的表型，可能具有共同的遗传原因：我们分析了6021名有冠状动脉造影、基因分型和外显子组测序数据的患者。我们检测了冠心病多基因风险评分（PRSCHD）与多种冠状动脉疾病（CAD）严重程度的相关性。我们评估了 PRSCHD 与 3 个家族性高胆固醇血症基因中的致病/可能致病变异之间的相互作用。我们进行了中介分析，以探讨CAD严重程度是否中介了PRSCHD与冠心病发病率和心肌梗死事件的关联：结果：PRSCHD增加1-SD与多种CAD严重程度相关，包括对数Gensini评分（β，0.31 [95% CI，0.28-0.33]）。在对 PRSCHD 进行调整后，携带致病性/可能致病性家族性高胆固醇血症变异与较高的对数 Gensini 评分相关（β，0.21 [95% CI，0.03-0.38]）。在平均9.2年的随访中，PRSCHD与心肌梗死事件相关（危险比为1.20 [95% CI, 1.13-1.27]；P=5×10-10），Gensini评分介导了90%的相关性：结论：PRSCHD与多种CAD严重程度相关。结论：PRSCHD与多种CAD严重程度相关，PRSCHD与心肌梗死事件的关联几乎完全由CAD严重程度介导，这表明这两种表型之间存在相当大的遗传重叠。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Circulation: Genomic and Precision Medicine Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

9.20

自引率

5.40%

发文量

144

期刊介绍： Circulation: Genomic and Precision Medicine is a distinguished journal dedicated to advancing the frontiers of cardiovascular genomics and precision medicine. It publishes a diverse array of original research articles that delve into the genetic and molecular underpinnings of cardiovascular diseases. The journal's scope is broad, encompassing studies from human subjects to laboratory models, and from in vitro experiments to computational simulations. Circulation: Genomic and Precision Medicine is committed to publishing studies that have direct relevance to human cardiovascular biology and disease, with the ultimate goal of improving patient care and outcomes. The journal serves as a platform for researchers to share their groundbreaking work, fostering collaboration and innovation in the field of cardiovascular genomics and precision medicine.