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

FinnGen; Linda Ottensmann; Rubina Tabassum; Sanni E. Ruotsalainen; Mathias J. Gerl; Christian Klose; Elisabeth Widén; Kai Simons; Samuli Ripatti; Matti Pirinen; Mikko Arvas; Kati Hyvärinen; Jarmo Ritari; Jukka Partanen

doi:10.1038/s41467-023-42532-8

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

FinnGen, Linda Ottensmann, Rubina Tabassum, Sanni E. Ruotsalainen, Mathias J. Gerl, Christian Klose, Elisabeth Widén, Kai Simons, Samuli Ripatti, Matti Pirinen, Mikko Arvas, Kati Hyvärinen, Jarmo Ritari, Jukka Partanen

Research output: Contribution to journal › Article › Scientific › peer-review

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.

Original language	English
Article number	6934
Journal	Nature Communications
Volume	14
Issue number	1
Number of pages	15
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-023-42532-8
Publication status	Published - 31 Oct 2023
MoE publication type	A1 Journal article-refereed

Fields of Science

1184 Genetics, developmental biology, physiology

Access to Document

10.1038/s41467-023-42532-8Licence: CC BY

s41467-023-42532-8Final published version, 1.12 MBLicence: CC BY

Cite this

FinnGen, Ottensmann, L., Tabassum, R., Ruotsalainen, S. E., Gerl, M. J., Klose, C., Widén, E., Simons, K., Ripatti, S., Pirinen, M., Arvas, M., Hyvärinen, K., Ritari, J., & Partanen, J. (2023). Genome-wide association analysis of plasma lipidome identifies 495 genetic associations. Nature Communications, 14(1), Article 6934. https://doi.org/10.1038/s41467-023-42532-8

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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.",

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