IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-42532-8.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-42532-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-42532-8?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Natalie DeForest & Yuqi Wang & Zhiyi Zhu & Jacqueline S. Dron & Ryan Koesterer & Pradeep Natarajan & Jason Flannick & Tiffany Amariuta & Gina M. Peloso & Amit R. Majithia, 2024. "Genome-wide discovery and integrative genomic characterization of insulin resistance loci using serum triglycerides to HDL-cholesterol ratio as a proxy," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. William R. Reay & Dylan J. Kiltschewskij & Maria A. Biase & Zachary F. Gerring & Kousik Kundu & Praveen Surendran & Laura A. Greco & Erin D. Clarke & Clare E. Collins & Alison M. Mondul & Demetrius Al, 2024. "Genetic influences on circulating retinol and its relationship to human health," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Shuai Yuan & Jie Chen & Jiawei Geng & Sizheng Steven Zhao & James Yarmolinsky & Elizabeth V. Arkema & Sarah Abramowitz & Michael G. Levin & Kostas K. Tsilidis & Stephen Burgess & Scott M. Damrauer & S, 2025. "GWAS identifies genetic loci, lifestyle factors and circulating biomarkers that are risk factors for sarcoidosis," Nature Communications, Nature, vol. 16(1), pages 1-11, December.
    4. Tzu-Ting Chen & Jaeyoung Kim & Max Lam & Yi-Fang Chuang & Yen-Ling Chiu & Shu-Chin Lin & Sang-Hyuk Jung & Beomsu Kim & Soyeon Kim & Chamlee Cho & Injeong Shim & Sanghyeon Park & Yeeun Ahn & Aysu Okbay, 2024. "Shared genetic architectures of educational attainment in East Asian and European populations," Nature Human Behaviour, Nature, vol. 8(3), pages 562-575, March.
    5. Hongru Li & Jingyi Zhao & Jinglan Dai & Dongfang You & Yang Zhao & David C. Christiani & Feng Chen & Sipeng Shen, 2025. "Multi-ancestry sequencing-based genome-wide association study of C-reactive protein in 513,273 genomes," Nature Communications, Nature, vol. 16(1), pages 1-11, December.
    6. Xiao-Yu He & Bang-Sheng Wu & Liu Yang & Yu Guo & Yue-Ting Deng & Ze-Yu Li & Chen-Jie Fei & Wei-Shi Liu & Yi-Jun Ge & Jujiao Kang & Jianfeng Feng & Wei Cheng & Qiang Dong & Jin-Tai Yu, 2024. "Genetic associations of protein-coding variants in venous thromboembolism," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    7. Javier Botey-Bataller & Hedwig D. Vrijmoeth & Jeanine Ursinus & Bart-Jan Kullberg & Cees C. Wijngaard & Hadewych Hofstede & Ahmed Alaswad & Manoj K. Gupta & Lennart M. Roesner & Jochen Huehn & Thomas , 2024. "A comprehensive genetic map of cytokine responses in Lyme borreliosis," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    8. Caitlin E. Carey & Rebecca Shafee & Robbee Wedow & Amanda Elliott & Duncan S. Palmer & John Compitello & Masahiro Kanai & Liam Abbott & Patrick Schultz & Konrad J. Karczewski & Samuel C. Bryant & Caro, 2024. "Principled distillation of UK Biobank phenotype data reveals underlying structure in human variation," Nature Human Behaviour, Nature, vol. 8(8), pages 1599-1615, August.
    9. Ichcha Manipur & Guillermo Reales & Jae Hoon Sul & Myung Kyun Shin & Simonne Longerich & Adrian Cortes & Chris Wallace, 2024. "CoPheScan: phenome-wide association studies accounting for linkage disequilibrium," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    10. Anand E. Rajesh & Abraham Olvera-Barrios & Alasdair N. Warwick & Yue Wu & Kelsey V. Stuart & Mahantesh I. Biradar & Chuin Ying Ung & Anthony P. Khawaja & Robert Luben & Paul J. Foster & Charles R. Cle, 2025. "Machine learning derived retinal pigment score from ophthalmic imaging shows ethnicity is not biology," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    11. Liang-Dar Hwang & Gabriel Cuellar-Partida & Loic Yengo & Jian Zeng & Jarkko Toivonen & Mikko Arvas & Robin N. Beaumont & Rachel M. Freathy & Gunn-Helen Moen & Nicole M. Warrington & David M. Evans, 2024. "DINGO: increasing the power of locus discovery in maternal and fetal genome-wide association studies of perinatal traits," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    12. Jeewoo Kim & Ariel Williams & Hannah Noh & Elizabeth A. Jasper & Sarah H. Jones & James A. Jaworski & Megan M. Shuey & Edward A. Ruiz-Narváez & Lauren A. Wise & Julie R. Palmer & John Connolly & Jacob, 2025. "Genome-wide meta-analysis identifies novel risk loci for uterine fibroids within and across multiple ancestry groups," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    13. Anders Gummesson & Per Lundmark & Qiao Sen Chen & Elias Björnson & Koen F. Dekkers & Ulf Hammar & Martin Adiels & Yunzhang Wang & Therese Andersson & Göran Bergström & Carl-Johan Carlhäll & David Erli, 2025. "A genome-wide association study of imaging-defined atherosclerosis," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    14. Xianyong Yin & Jack Li & Debraj Bose & Jeffrey Okamoto & Annie Kwon & Anne U. Jackson & Lilian Fernandes Silva & Anniina Oravilahti & Xiaomeng Chu & Heather M. Stringham & Lei Liu & Ruyi Peng & Zhijie, 2025. "Assessing the potential causal effects of 1099 plasma metabolites on 2099 binary disease endpoints," Nature Communications, Nature, vol. 16(1), pages 1-10, December.
    15. Jujiao Kang & Yue-Ting Deng & Bang-Sheng Wu & Wei-Shi Liu & Ze-Yu Li & Shitong Xiang & Liu Yang & Jia You & Xiaohong Gong & Tianye Jia & Jin-Tai Yu & Wei Cheng & Jianfeng Feng, 2024. "Whole exome sequencing analysis identifies genes for alcohol consumption," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    16. Salim Megat & Christine Marques & Marina Hernán-Godoy & Chantal Sellier & Geoffrey Stuart-Lopez & Sylvie Dirrig-Grosch & Charlotte Gorin & Aurore Brunet & Mathieu Fischer & Céline Keime & Pascal Kessl, 2025. "CREB3 gain of function variants protect against ALS," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    17. Xingjie Hao & Zhonghe Shao & Ning Zhang & Minghui Jiang & Xi Cao & Si Li & Yunlong Guan & Chaolong Wang, 2023. "Integrative genome-wide analyses identify novel loci associated with kidney stones and provide insights into its genetic architecture," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    18. Ruoyu Tian & Tian Ge & Hyeokmoon Kweon & Daniel B. Rocha & Max Lam & Jimmy Z. Liu & Kritika Singh & Daniel F. Levey & Joel Gelernter & Murray B. Stein & Ellen A. Tsai & Hailiang Huang & Christopher F., 2024. "Whole-exome sequencing in UK Biobank reveals rare genetic architecture for depression," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    19. Isabelle Austin-Zimmerman & Daniel F. Levey & Olga Giannakopoulou & Joseph D. Deak & Marco Galimberti & Keyrun Adhikari & Hang Zhou & Spiros Denaxas & Haritz Irizar & Karoline Kuchenbaecker & Andrew M, 2023. "Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    20. Saedis Saevarsdottir & Kristbjörg Bjarnadottir & Thorsteinn Markusson & Jonas Berglund & Thorunn A. Olafsdottir & Gisli H. Halldorsson & Gudrun Rutsdottir & Kristbjorg Gunnarsdottir & Asgeir Orn Arnth, 2024. "Start codon variant in LAG3 is associated with decreased LAG-3 expression and increased risk of autoimmune thyroid disease," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42532-8. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.