Genome-wide association analysis of plasma lipidome identifies 495 genetic associations

Human plasma lipidome captures risk for cardio-metabolic diseases. To discover new lipid-associated variants and understand link between lipid species and cardiometabolic disorders, we performed univariate and multivariate genome-wide analyses of 179 lipid species in 7,174 Finnish individuals. We further fine-mapped the associated loci, prioritized genes, and examined their disease links in 377,277 FinnGen participants. We identified 495 genome-trait associations in 56 genetic loci including 9 novel loci, with a considerable boost provided by multivariate analysis. For 26 loci, fine-mapping identified variants with a high causal probability, including 14 coding variants indicating likely causal genes. Phenome-wide analysis across 953 disease endpoints in FinnGen revealed disease associations for 40 lipid loci. For 11 known coronary artery disease risk variants, we detected strong associations with lipid species. Our study demonstrates the power of multivariate genetic analysis in correlated lipidomics data and reveals genetic links between diseases and detailed lipid measures beyond standard lipids.