Genome-wide Pleiotropy Analysis of Coronary Artery Disease and Pneumonia Identifies Shared Immune Pathways

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2022 Apr 22

PMID 35452290

Authors

Zhi Yu

Seyedeh M Zekavat

Sara Haidermota

Rachel Bernardo

Bryan T MacDonald

Peter Libby

Hilary K Finucane

Pradeep Natarajan

Affiliations

Soon will be listed here.

Abstract

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.

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