biostudies-literatureUnknown3(11)Kain JCoronary 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 instrumentalCell reports. Medicine100805https://www.ebi.ac.uk/biostudies/studies/S-EPMC9729823biostudies-literatureMendelian randomization and pathway analysis demonstrate shared genetic associations between lupus and coronary artery disease.PMC9729823Langefeld CDMarion MCKain JLipsky PEOwen KAGrammer ACfalseMendelian randomization and pathway analysis demonstrate shared genetic associations between lupus and coronary artery disease.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 instrumental2022-01-01T00:00:00Z2022 Nov2026-05-28T02:58:00.091Z2025-04-19T12:11:14.451ZS-EPMC97298233633459210.1016/j.xcrm.2022.100805