IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-58129-2.html
   My bibliography  Save this article

Assessing the potential causal effects of 1099 plasma metabolites on 2099 binary disease endpoints

Author

Listed:
  • Xianyong Yin

    (Nanjing Medical University)

  • Jack Li

    (University of Michigan School of Public Health)

  • Debraj Bose

    (University of Michigan School of Public Health)

  • Jeffrey Okamoto

    (University of Michigan School of Public Health)

  • Annie Kwon

    (University of Michigan School of Public Health)

  • Anne U. Jackson

    (University of Michigan School of Public Health)

  • Lilian Fernandes Silva

    (University of Eastern Finland and Kuopio University Hospital)

  • Anniina Oravilahti

    (University of Eastern Finland and Kuopio University Hospital)

  • Xiaomeng Chu

    (Nanjing Medical University)

  • Heather M. Stringham

    (University of Michigan School of Public Health)

  • Lei Liu

    (Nanjing Medical University)

  • Ruyi Peng

    (Nanjing Medical University)

  • Zhijie Xia

    (Nanjing Medical University)

  • Samuli Ripatti

    (University of Helsinki
    University of Helsinki
    Broad Institute of MIT & Harvard)

  • Mark Daly

    (University of Helsinki
    University of Helsinki
    Massachusetts General Hospital)

  • Aarno Palotie

    (University of Helsinki
    University of Helsinki
    Massachusetts General Hospital)

  • Laura J. Scott

    (University of Michigan School of Public Health)

  • Charles F. Burant

    (University of Michigan)

  • Eric B. Fauman

    (Development and Medical)

  • Xiaoquan Wen

    (University of Michigan School of Public Health)

  • Michael Boehnke

    (University of Michigan School of Public Health)

  • Markku Laakso

    (University of Eastern Finland and Kuopio University Hospital)

  • Jean Morrison

    (University of Michigan School of Public Health)

Abstract

Metabolites are small molecules that are useful for estimating disease risk and elucidating disease biology. Here, we perform two-sample Mendelian randomization to systematically infer the potential causal effects of 1099 plasma metabolites measured in 6136 Finnish men from the METSIM study on risk of 2099 binary disease endpoints measured in 309,154 Finnish individuals from FinnGen. We find evidence for 282 putative causal effects of 70 metabolites on 183 disease endpoints. We also identify 25 metabolites with potential causal effects across multiple disease domains, including ascorbic acid 2-sulfate affecting 26 disease endpoints in 12 disease domains. Our study suggests that N-acetyl-2-aminooctanoate and glycocholenate sulfate affect risk of atrial fibrillation through two distinct metabolic pathways and that N-methylpipecolate may mediate the putative causal effect of N6,N6-dimethyllysine on anxious personality disorder.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58129-2
    DOI: 10.1038/s41467-025-58129-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-58129-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-58129-2?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
    ---><---

    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:16:y:2025:i:1:d:10.1038_s41467-025-58129-2. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.