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

Author

Listed:
  • 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
    University of Helsinki
    Broad Institute of the Massachusetts Institute of Technology and Harvard University)

  • Matti Pirinen

    (University of Helsinki
    University of Helsinki
    University of Helsinki)

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.

Suggested Citation

  • Linda Ottensmann & Rubina Tabassum & Sanni E. Ruotsalainen & Mathias J. Gerl & Christian Klose & Elisabeth Widén & Kai Simons & Samuli Ripatti & Matti Pirinen, 2023. "Genome-wide association analysis of plasma lipidome identifies 495 genetic associations," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42532-8
    DOI: 10.1038/s41467-023-42532-8
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    1. Tanya M. Teslovich & Kiran Musunuru & Albert V. Smith & Andrew C. Edmondson & Ioannis M. Stylianou & Masahiro Koseki & James P. Pirruccello & Samuli Ripatti & Daniel I. Chasman & Cristen J. Willer & C, 2010. "Biological, clinical and population relevance of 95 loci for blood lipids," Nature, Nature, vol. 466(7307), pages 707-713, August.
    2. Rubina Tabassum & Joel T. Rämö & Pietari Ripatti & Jukka T. Koskela & Mitja Kurki & Juha Karjalainen & Priit Palta & Shabbeer Hassan & Javier Nunez-Fontarnau & Tuomo T. J. Kiiskinen & Sanni Söderlund , 2019. "Genetic architecture of human plasma lipidome and its link to cardiovascular disease," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    3. B. Devlin & Kathryn Roeder, 1999. "Genomic Control for Association Studies," Biometrics, The International Biometric Society, vol. 55(4), pages 997-1004, December.
    4. Xianyong Yin & Lap Sum Chan & Debraj Bose & Anne U. Jackson & Peter VandeHaar & Adam E. Locke & Christian Fuchsberger & Heather M. Stringham & Ryan Welch & Ketian Yu & Lilian Fernandes Silva & Susan K, 2022. "Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    5. Alvaro N Barbeira & Milton Pividori & Jiamao Zheng & Heather E Wheeler & Dan L Nicolae & Hae Kyung Im, 2019. "Integrating predicted transcriptome from multiple tissues improves association detection," PLOS Genetics, Public Library of Science, vol. 15(1), pages 1-20, January.
    6. Apolline Gallois & Joel Mefford & Arthur Ko & Amaury Vaysse & Hanna Julienne & Mika Ala-Korpela & Markku Laakso & Noah Zaitlen & Päivi Pajukanta & Hugues Aschard, 2019. "A comprehensive study of metabolite genetics reveals strong pleiotropy and heterogeneity across time and context," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    7. Mitja I. Kurki & Juha Karjalainen & Priit Palta & Timo P. Sipilä & Kati Kristiansson & Kati M. Donner & Mary P. Reeve & Hannele Laivuori & Mervi Aavikko & Mari A. Kaunisto & Anu Loukola & Elisa Lahtel, 2023. "Author Correction: FinnGen provides genetic insights from a well-phenotyped isolated population," Nature, Nature, vol. 615(7952), pages 19-19, March.
    8. Kyoko Watanabe & Erdogan Taskesen & Arjen Bochoven & Danielle Posthuma, 2017. "Functional mapping and annotation of genetic associations with FUMA," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    9. Gao Wang & Abhishek Sarkar & Peter Carbonetto & Matthew Stephens, 2020. "A simple new approach to variable selection in regression, with application to genetic fine mapping," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 82(5), pages 1273-1300, December.
    10. Karsten Suhre & So-Youn Shin & Ann-Kristin Petersen & Robert P. Mohney & David Meredith & Brigitte Wägele & Elisabeth Altmaier & Panos Deloukas & Jeanette Erdmann & Elin Grundberg & Christopher J. Ham, 2011. "Human metabolic individuality in biomedical and pharmaceutical research," Nature, Nature, vol. 477(7362), pages 54-60, September.
    11. Sarah E. Graham & Shoa L. Clarke & Kuan-Han H. Wu & Stavroula Kanoni & Greg J. M. Zajac & Shweta Ramdas & Ida Surakka & Ioanna Ntalla & Sailaja Vedantam & Thomas W. Winkler & Adam E. Locke & Eirini Ma, 2021. "The power of genetic diversity in genome-wide association studies of lipids," Nature, Nature, vol. 600(7890), pages 675-679, December.
    12. Mitja I. Kurki & Juha Karjalainen & Priit Palta & Timo P. Sipilä & Kati Kristiansson & Kati M. Donner & Mary P. Reeve & Hannele Laivuori & Mervi Aavikko & Mari A. Kaunisto & Anu Loukola & Elisa Lahtel, 2023. "FinnGen provides genetic insights from a well-phenotyped isolated population," Nature, Nature, vol. 613(7944), pages 508-518, January.
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