Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Colocalization highlights genes in hypothalamic–pituitary–gonadal axis as potentially mediating polycystic ovary syndrome risk

View ORCID ProfileJenny C Censin, View ORCID ProfileJonas Bovijn, View ORCID ProfileMichael V Holmes, View ORCID ProfileCecilia M Lindgren
doi: https://doi.org/10.1101/2020.01.10.901116
Jenny C Censin
1Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, OX3 7LF, UK
2Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jenny C Censin
  • For correspondence: jenny.censin@ndm.ox.ac.uk
Jonas Bovijn
1Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, OX3 7LF, UK
2Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jonas Bovijn
Michael V Holmes
3NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, OX3 9DU, UK
4Medical Research Council Population Health Research Unit at the University of Oxford, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK
5Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, Big Data Institute Building, Roosevelt Drive, University of Oxford, Oxford, OX3 7LF, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Michael V Holmes
Cecilia M Lindgren
1Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, OX3 7LF, UK
2Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK
3NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, OX3 9DU, UK
6Program in Medical and Population Genetics, Broad Institute, Cambridge, 02142, Massachusetts, USA
7Nuffield Department of Women’s and Reproductive Health, University of Oxford, Oxford, OX3 9DU, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Cecilia M Lindgren
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Polycystic ovary syndrome (PCOS) is a common disease in women with consequences for reproductive, metabolic and psychological health. Women with PCOS have disrupted signalling in the hypothalamic-pituitary-gonadal axis and studies have indicated that the disease has a large genetic component. While a recent genome-wide association study of PCOS performed in up to 10,074 cases and 103,164 controls of European decent identified 14 PCOS-associated regions, much of the disease pathophysiology remains unclear.

Here, we use a Bayesian colocalization approach to highlight genes that may have a potential role in PCOS pathophysiology and thus are of particular interest for further functional follow-up. We evaluated the posterior probabilities of shared causal variants between PCOS genetic risk loci and intermediate cellular phenotypes in one protein and two expression quantitative trait locus datasets, respectively. Sample sizes ranged from 80 to 31,684. In total, we identified seven proteins or genes with evidence of a shared causal variant for almost a third of PCOS signals, including follicle stimulating hormone (FSH) and the genes ERBB3, IKZF4, RPS26, SUOX, ZFP36L2, and C8orf49. Several of these genes and proteins have been implicated in the hypothalamic-pituitary-gonadal signalling pathway.

In summary, our results suggest potential effector proteins and genes for PCOS association signals. This highlights genes for functional follow-up in order to demonstrate a causal role in PCOS pathophysiology.

  • Abbreviations

    eQTL
    expression quantitative trait locus
    FSH
    follicle-stimulating hormone
    GnRH
    gonadotropin-releasing hormone
    GTEx
    Genotype-Tissue Expression project
    GWAS
    genome-wide association study
    HPG
    hypothalamic-pituitary-gonadal
    LH
    luteinizing hormone
    PCOS
    polycystic ovary syndrome
    PheWAS
    phenome-wide association study
    PP
    posterior probability
    pQTL
    protein quantitative trait locus
    SNP
    single nucleotide polymorphism
  • Copyright 
    The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
    Back to top
    PreviousNext
    Posted January 10, 2020.
    Download PDF

    Supplementary Material

    Email

    Thank you for your interest in spreading the word about bioRxiv.

    NOTE: Your email address is requested solely to identify you as the sender of this article.

    Enter multiple addresses on separate lines or separate them with commas.
    Colocalization highlights genes in hypothalamic–pituitary–gonadal axis as potentially mediating polycystic ovary syndrome risk
    (Your Name) has forwarded a page to you from bioRxiv
    (Your Name) thought you would like to see this page from the bioRxiv website.
    CAPTCHA
    This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
    Share
    Colocalization highlights genes in hypothalamic–pituitary–gonadal axis as potentially mediating polycystic ovary syndrome risk
    Jenny C Censin, Jonas Bovijn, Michael V Holmes, Cecilia M Lindgren
    bioRxiv 2020.01.10.901116; doi: https://doi.org/10.1101/2020.01.10.901116
    Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
    Citation Tools
    Colocalization highlights genes in hypothalamic–pituitary–gonadal axis as potentially mediating polycystic ovary syndrome risk
    Jenny C Censin, Jonas Bovijn, Michael V Holmes, Cecilia M Lindgren
    bioRxiv 2020.01.10.901116; doi: https://doi.org/10.1101/2020.01.10.901116

    Citation Manager Formats

    • BibTeX
    • Bookends
    • EasyBib
    • EndNote (tagged)
    • EndNote 8 (xml)
    • Medlars
    • Mendeley
    • Papers
    • RefWorks Tagged
    • Ref Manager
    • RIS
    • Zotero
    • Tweet Widget
    • Facebook Like
    • Google Plus One

    Subject Area

    • Genetics
    Subject Areas
    All Articles
    • Animal Behavior and Cognition (4118)
    • Biochemistry (8825)
    • Bioengineering (6529)
    • Bioinformatics (23481)
    • Biophysics (11802)
    • Cancer Biology (9221)
    • Cell Biology (13334)
    • Clinical Trials (138)
    • Developmental Biology (7442)
    • Ecology (11421)
    • Epidemiology (2066)
    • Evolutionary Biology (15169)
    • Genetics (10449)
    • Genomics (14054)
    • Immunology (9184)
    • Microbiology (22186)
    • Molecular Biology (8821)
    • Neuroscience (47615)
    • Paleontology (350)
    • Pathology (1431)
    • Pharmacology and Toxicology (2492)
    • Physiology (3736)
    • Plant Biology (8085)
    • Scientific Communication and Education (1438)
    • Synthetic Biology (2222)
    • Systems Biology (6042)
    • Zoology (1254)