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

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. W...

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Bibliographic Details
Published in:Nature communications Vol. 14; no. 1; pp. 6934 - 15
Main Authors: Ottensmann, Linda, Tabassum, Rubina, Ruotsalainen, Sanni E., Gerl, Mathias J., Klose, Christian, Widén, Elisabeth, Simons, Kai, Ripatti, Samuli, Pirinen, Matti
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 31.10.2023
Nature Publishing Group
Nature Portfolio
Subjects:
140/58
45/43
631/114/2163
631/208/205/2138
631/443/319/2723
692/499
Association analysis
Blood plasma
Cardiovascular disease
Cholesterol
Coronary artery disease
Gene loci
Gene mapping
Genes
Genetic analysis
Genomes
Health risks
Heart diseases
High density lipoprotein
Humanities and Social Sciences
Links
Lipids
Low density lipoprotein
multidisciplinary
Multivariate analysis
Risk
Science
Science (multidisciplinary)
Species
Triglycerides
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary: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. The human plasma lipidome captures risk for cardiometabolic diseases. Here, the authors perform univariate and multivariate genome-wide analyses of 179 lipid species in 7174 Finnish individuals, revealing genetic links between diseases and lipid species beyond the standard lipids HDL-Cholesterol, LDL-Cholesterol, Triglycerides, and total Cholesterol.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-023-42532-8