一项关于冠状动脉疾病和亚临床动脉粥样硬化特征的多性状全基因组关联研究。

A multi-trait genome-wide association study of coronary artery disease and subclinical atherosclerosis traits.

作者信息

de Vries Paul, Hasbani Natalie, Heath Adam, Hodonsky Chani, Hahn Julie, Meena Devendra, Lu Haojie, Dehghan Abbas Abbas, Kavousi Maryam, Voight Benjamin, Peyser Patricia, Morrison Alanna, Assimes Themistocles, Damrauer Scott, Miller Clint

机构信息

Human Genetics Center.

The University of Texas Health Science Center at Houston.

出版信息

Res Sq. 2025 Apr 21:rs.3.rs-6456056. doi: 10.21203/rs.3.rs-6456056/v1.

DOI:10.21203/rs.3.rs-6456056/v1

PMID:40313769

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12045367/

Abstract

Measures of subclinical atherosclerosis, such as coronary artery calcification (CAC) and carotid intima-media thickness (CIMT), reflect the underlying pathophysiology of coronary artery disease (CAD) and are genetically correlated with CAD and related risk factors. Leveraging summary statistics from genome-wide association studies of CAD, CIMT, CAC, type 2 diabetes, low-density lipoprotein cholesterol, and systolic blood pressure, we performed 15 separate multi-trait GWAS to identify shared susceptibility loci and elucidate the pleiotropic architecture underlying atherosclerosis. We identified 442 shared risk loci across all analyses that met an experiment-wide Bonferroni threshold of 3.3 × 10, uncovering 195 novel atherosclerosis loci. Multi-trait colocalization confirmed a shared causal signal in 25 shared novel loci for atherosclerosis. Trait-eQTL colocalization identified evidence of a shared causal signal in arterial, subcutaneous adipose, and cardiac tissues, implicating genes such as , , , , and , and pathways related to vascular remodeling, inflammation, and metabolic regulation.

摘要

亚临床动脉粥样硬化的指标，如冠状动脉钙化（CAC）和颈动脉内膜中层厚度（CIMT），反映了冠状动脉疾病（CAD）的潜在病理生理学，并且与CAD及相关危险因素存在遗传相关性。利用CAD、CIMT、CAC、2型糖尿病、低密度脂蛋白胆固醇和收缩压的全基因组关联研究的汇总统计数据，我们进行了15项独立的多性状全基因组关联研究，以识别共同的易感基因座，并阐明动脉粥样硬化潜在的多效性结构。我们在所有分析中确定了442个符合全实验范围Bonferroni阈值3.3×10的共同风险基因座，发现了195个新的动脉粥样硬化基因座。多性状共定位在25个共同的新动脉粥样硬化基因座中证实了一个共同的因果信号。性状-表达数量性状基因座共定位在动脉、皮下脂肪和心脏组织中发现了共同因果信号的证据，涉及、、、和等基因，以及与血管重塑炎症和代谢调节相关的通路。