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    Genome-wide cross-disease analyses highlight causality and shared biological pathways of type 2 diabetes with gastrointestinal disorders

    Access Status
    In process
    Authors
    Adewuyi, Emmanuel
    Porter, T.
    O’Brien, E.K.
    Olaniru, O.
    Verdile, Giuseppe
    Laws, S.M.
    Date
    2024
    Type
    Journal Article
    
    Metadata
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    Citation
    Adewuyi, E.O. and Porter, T. and O’Brien, E.K. and Olaniru, O. and Verdile, G. and Laws, S.M. 2024. Genome-wide cross-disease analyses highlight causality and shared biological pathways of type 2 diabetes with gastrointestinal disorders. Communications Biology. 7 (1): pp. 643-.
    Source Title
    Communications Biology
    DOI
    10.1038/s42003-024-06333-z
    ISSN
    2399-3642
    Faculty
    Faculty of Health Sciences
    Faculty of Health Sciences
    School
    Curtin School of Population Health
    Curtin Medical School
    URI
    http://hdl.handle.net/20.500.11937/97663
    Collection
    • Curtin Research Publications
    Abstract

    Studies suggest links between diabetes and gastrointestinal (GI) traits; however, their underlying biological mechanisms remain unclear. Here, we comprehensively assess the genetic relationship between type 2 diabetes (T2D) and GI disorders. Our study demonstrates a significant positive global genetic correlation of T2D with peptic ulcer disease (PUD), irritable bowel syndrome (IBS), gastritis-duodenitis, gastroesophageal reflux disease (GERD), and diverticular disease, but not inflammatory bowel disease (IBD). We identify several positive local genetic correlations (negative for T2D – IBD) contributing to T2D’s relationship with GI disorders. Univariable and multivariable Mendelian randomisation analyses suggest causal effects of T2D on PUD and gastritis-duodenitis and bidirectionally with GERD. Gene-based analyses reveal a gene-level genetic overlap between T2D and GI disorders and identify several shared genes reaching genome-wide significance. Pathway-based study implicates leptin (T2D – IBD), thyroid, interferon, and notch signalling (T2D – IBS), abnormal circulating calcium (T2D – PUD), cardiovascular, viral, proinflammatory and (auto)immune-mediated mechanisms in T2D and GI disorders. These findings support a risk-increasing genetic overlap between T2D and GI disorders (except IBD), implicate shared biological pathways with putative causality for certain T2D – GI pairs, and identify targets for further investigation.

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