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Sci Adv DOI:10.1126/sciadv.abl4602

Genome-wide pleiotropy analysis of coronary artery disease and pneumonia identifies shared immune pathways.

Publication TypeJournal Article
Year of Publication2022
AuthorsYu, Z, Zekavat, SM, Haidermota, S, Bernardo, R, MacDonald, BT, Libby, P, Finucane, HK, Natarajan, P
JournalSci Adv
Date Published2022 Apr 22
KeywordsADAMTS7 Protein, Coronary Artery Disease, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Pneumonia, Polymorphism, Single Nucleotide

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 and . Increased expression across tissues consistently showed decreased risk for CAD and increased risk for pneumonia; increased expression showed increased risk for CAD and decreased risk for pneumonia. We similarly observed opposing CAD/pneumonia effects for . Reduced 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 and , and related genes.


Alternate JournalSci Adv
PubMed ID35452290