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

Linda Ottensmann (), Rubina Tabassum, Sanni E. Ruotsalainen, Mathias J. Gerl, Christian Klose, Elisabeth Widén, Kai Simons, Samuli Ripatti and Matti Pirinen ()
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Linda Ottensmann: University of Helsinki
Rubina Tabassum: University of Helsinki
Sanni E. Ruotsalainen: University of Helsinki
Mathias J. Gerl: Lipotype GmbH
Christian Klose: Lipotype GmbH
Elisabeth Widén: University of Helsinki
Kai Simons: Lipotype GmbH
Samuli Ripatti: University of Helsinki
Matti Pirinen: University of Helsinki

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract The human plasma lipidome captures risk for cardiometabolic diseases. To discover new lipid-associated variants and understand the link between lipid species and cardiometabolic disorders, we perform univariate and multivariate genome-wide analyses of 179 lipid species in 7174 Finnish individuals. We fine-map the associated loci, prioritize genes, and examine their disease links in 377,277 FinnGen participants. We identify 495 genome-trait associations in 56 genetic loci including 8 novel loci, with a considerable boost provided by the multivariate analysis. For 26 loci, fine-mapping identifies variants with a high causal probability, including 14 coding variants indicating likely causal genes. A phenome-wide analysis across 953 disease endpoints reveals disease associations for 40 lipid loci. For 11 coronary artery disease risk variants, we detect 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 lipid species beyond the standard lipids.

Date: 2023
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DOI: 10.1038/s41467-023-42532-8

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