Work

Mendelian randomization and pathway analysis demonstrate shared genetic associations between lupus and coronary artery disease

Year: 2022

Type: article

Abstract: Coronary artery disease (CAD) is a leading cause of death in patients with systemic lupus erythematosus (SLE). Despite clinical evidence supporting an association between SLE and CAD, pleiotropy-adjusted genetic association studies are limited and focus on only a few common risk loci. Here, we identify a net positive causal estimate of SLE-associated non-HLA SNPs on CAD by traditional Mendelian randomization (MR) approaches. Pathway analysis using SNP-to-gene mapping followed by unsupervised clustering based on protein-protein interactions (PPIs) identifies biological networks composed of positive and negative causal sets of genes. In addition, we confirm the casual effects of specific SNP-to-gene modules on CAD using only SNP mapping to each PPI-defined functional gene set as instrumental variables. This PPI-based MR approach elucidates various molecular pathways with causal implications between SLE and CAD and identifies biological pathways likely causative of both pathologies, revealing known and novel therapeutic interventions for managing CAD in SLE.

Source: Cell Reports Medicine

DOI: 10.1016/j.xcrm.2022.100805

Authors: Jessica Kain, Katherine A. Owen, Miranda C. Marion, Carl D. Langefeld, Amrie C. Grammer, Peter E. Lipsky

Institutions: Ampel BioSolutions (United States), Wake Forest University Health Sciences, Wake Forest University

Language: English

Topic: Genetic Associations and Epidemiology

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $5,200