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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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Autores principales: Ottensmann, Linda, Tabassum, Rubina, Ruotsalainen, Sanni E., Gerl, Mathias J., Klose, Christian, Widén, Elisabeth, Simons, Kai, Ripatti, Samuli, Pirinen, Matti
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618167/
https://www.ncbi.nlm.nih.gov/pubmed/37907536
http://dx.doi.org/10.1038/s41467-023-42532-8
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author Ottensmann, Linda
Tabassum, Rubina
Ruotsalainen, Sanni E.
Gerl, Mathias J.
Klose, Christian
Widén, Elisabeth
Simons, Kai
Ripatti, Samuli
Pirinen, Matti
author_facet Ottensmann, Linda
Tabassum, Rubina
Ruotsalainen, Sanni E.
Gerl, Mathias J.
Klose, Christian
Widén, Elisabeth
Simons, Kai
Ripatti, Samuli
Pirinen, Matti
author_sort Ottensmann, Linda
collection PubMed
description 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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spelling pubmed-106181672023-11-02 Genome-wide association analysis of plasma lipidome identifies 495 genetic associations Ottensmann, Linda Tabassum, Rubina Ruotsalainen, Sanni E. Gerl, Mathias J. Klose, Christian Widén, Elisabeth Simons, Kai Ripatti, Samuli Pirinen, Matti Nat Commun Article 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. Nature Publishing Group UK 2023-10-31 /pmc/articles/PMC10618167/ /pubmed/37907536 http://dx.doi.org/10.1038/s41467-023-42532-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ottensmann, Linda
Tabassum, Rubina
Ruotsalainen, Sanni E.
Gerl, Mathias J.
Klose, Christian
Widén, Elisabeth
Simons, Kai
Ripatti, Samuli
Pirinen, Matti
Genome-wide association analysis of plasma lipidome identifies 495 genetic associations
title Genome-wide association analysis of plasma lipidome identifies 495 genetic associations
title_full Genome-wide association analysis of plasma lipidome identifies 495 genetic associations
title_fullStr Genome-wide association analysis of plasma lipidome identifies 495 genetic associations
title_full_unstemmed Genome-wide association analysis of plasma lipidome identifies 495 genetic associations
title_short Genome-wide association analysis of plasma lipidome identifies 495 genetic associations
title_sort genome-wide association analysis of plasma lipidome identifies 495 genetic associations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618167/
https://www.ncbi.nlm.nih.gov/pubmed/37907536
http://dx.doi.org/10.1038/s41467-023-42532-8
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