冠状动脉疾病
肺炎
多效性
生物
疾病
单核苷酸多态性
基因
免疫系统
生物信息学
遗传学
免疫学
医学
内科学
基因型
表型
作者
Zhi Gen Yu,Seyedeh M. Zekavat,Sara Haidermota,Rachel J. Bernardo,Bryan T. MacDonald,Peter Libby,Hilary K. Finucane,Pradeep Natarajan
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2022-04-22
卷期号:8 (16)
被引量:2
标识
DOI:10.1126/sciadv.abl4602
摘要
Coronary artery disease (CAD) remains the leading cause of death despite scientific advances. Elucidating shared CAD/pneumonia pathways may reveal novel insights regarding CAD pathways. We performed genome-wide pleiotropy analyses of CAD and pneumonia, examined the causal effects of the expression of genes near independently replicated SNPs and interacting genes with CAD and pneumonia, and tested interactions between disruptive coding mutations of each pleiotropic gene and smoking status on CAD and pneumonia risks. Identified pleiotropic SNPs were annotated to ADAMTS7 and IL6R . Increased ADAMTS7 expression across tissues consistently showed decreased risk for CAD and increased risk for pneumonia; increased IL6R expression showed increased risk for CAD and decreased risk for pneumonia. We similarly observed opposing CAD/pneumonia effects for NLRP3 . Reduced ADAMTS7 expression conferred a reduced CAD risk without increased pneumonia risk only among never-smokers. Genetic immune-inflammatory axes of CAD linked to respiratory infections implicate ADAMTS7 and IL6R , and related genes.
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