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

被引：80
作者：
Ottensmann L. [1 ]
Tabassum R. [1 ]
Ruotsalainen S.E. [1 ]
Gerl M.J. [2 ]
Klose C. [2 ]
Widén E. [1 ]
Simons K. [2 ]
Ripatti S. [1 ,3 ,4 ]
Pirinen M. [1 ,3 ,5 ]
机构：
[1] Institute for Molecular Medicine Finland, HiLIFE, University of Helsinki, Helsinki
[2] Lipotype GmbH, Dresden
[3] Department of Public Health, Clinicum, Faculty of Medicine, University of Helsinki, Helsinki
[4] Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA
[5] Department of Mathematics and Statistics, University of Helsinki, Helsinki
来源：
Nature Communications | / 14卷 / 1期
基金：
芬兰科学院;
关键词：
D O I：
10.1038/s41467-023-42532-8
中图分类号：
学科分类号：
摘要：
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. © 2023, The Author(s).
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