
Genome-wide pleiotropy analysis of coronary artery disease and pneumonia identifies shared immune pathways
Author(s) -
Zhi Yu,
Seyedeh M. Zekavat,
Sara Haidermota,
Rachel Bernardo,
Bryan T. MacDonald,
Peter Libby,
Hilary Finucane,
Pradeep Natarajan
Publication year - 2022
Publication title -
science advances
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.928
H-Index - 146
ISSN - 2375-2548
DOI - 10.1126/sciadv.abl4602
Subject(s) - coronary artery disease , pneumonia , pleiotropy , biology , disease , single nucleotide polymorphism , gene , immune system , bioinformatics , genetics , immunology , medicine , genotype , phenotype
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 toADAMTS7 andIL6R . IncreasedADAMTS7 expression across tissues consistently showed decreased risk for CAD and increased risk for pneumonia; increasedIL6R expression showed increased risk for CAD and decreased risk for pneumonia. We similarly observed opposing CAD/pneumonia effects forNLRP3 . ReducedADAMTS7 expression conferred a reduced CAD risk without increased pneumonia risk only among never-smokers. Genetic immune-inflammatory axes of CAD linked to respiratory infections implicateADAMTS7 andIL6R , and related genes.