IDEAS home Printed from https://ideas.repec.org/a/nat/nathum/v9y2025i2d10.1038_s41562-024-02045-w.html
   My bibliography  Save this article

Large-scale exome sequencing identified 18 novel genes for neuroticism in 394,005 UK-based individuals

Author

Listed:
  • Xin-Rui Wu

    (Fudan University)

  • Ze-Yu Li

    (Fudan University
    Fudan University, Ministry of Education)

  • Liu Yang

    (Fudan University)

  • Ying Liu

    (Fudan University)

  • Chen-Jie Fei

    (Fudan University)

  • Yue-Ting Deng

    (Fudan University)

  • Wei-Shi Liu

    (Fudan University)

  • Bang-Sheng Wu

    (Fudan University)

  • Qiang Dong

    (Fudan University)

  • Jian-Feng Feng

    (Fudan University
    Fudan University, Ministry of Education
    University of Warwick)

  • Wei Cheng

    (Fudan University
    Fudan University
    Fudan University, Ministry of Education)

  • Jin-Tai Yu

    (Fudan University)

Abstract

Existing genetic studies of neuroticism have been largely limited to common variants. Here we performed a large-scale exome analysis of white British individuals from UK Biobank, revealing the role of coding variants in neuroticism. For rare variants, collapsing analysis uncovered 14 neuroticism-associated genes. Among these, 12 (PTPRE, BCL10, TRIM32, ANKRD12, ADGRB2, MON2, HIF1A, ITGB2, STK39, CAPNS2, OGFOD1 and KDM4B) were novel, and the remaining (MADD and TRPC4AP) showed convergent evidence with common variants. Heritability of rare coding variants was estimated to be up to 7.3% for neuroticism. For common variants, we identified 78 significant associations, implicating 6 unreported genes. We subsequently replicated these variants using meta-analysis across other four ancestries from UK Biobank and summary data from 23andMe sample. Furthermore, these variants had widespread impacts on neuropsychiatric disorders, cognitive abilities and brain structure. Our findings deepen the understanding of neuroticism’s genetic architecture and provide potential targets for future mechanistic research.

Suggested Citation

  • Xin-Rui Wu & Ze-Yu Li & Liu Yang & Ying Liu & Chen-Jie Fei & Yue-Ting Deng & Wei-Shi Liu & Bang-Sheng Wu & Qiang Dong & Jian-Feng Feng & Wei Cheng & Jin-Tai Yu, 2025. "Large-scale exome sequencing identified 18 novel genes for neuroticism in 394,005 UK-based individuals," Nature Human Behaviour, Nature, vol. 9(2), pages 406-419, February.
    • Handle: RePEc:nat:nathum:v:9:y:2025:i:2:d:10.1038_s41562-024-02045-w
    DOI: 10.1038/s41562-024-02045-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41562-024-02045-w
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/s41562-024-02045-w?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    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:nathum:v:9:y:2025:i:2:d:10.1038_s41562-024-02045-w. 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.