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    A large-scale genome-wide cross-trait analysis reveals shared genetic architecture between Alzheimer’s disease and gastrointestinal tract disorders

    Access Status
    In process
    Authors
    Adewuyi, Emmanuel
    O’Brien, E.K.
    Nyholt, D.R.
    Porter, T.
    Laws, S.M.
    Date
    2022
    Type
    Journal Article
    
    Metadata
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    Citation
    Adewuyi, E.O. and O’Brien, E.K. and Nyholt, D.R. and Porter, T. and Laws, S.M. 2022. A large-scale genome-wide cross-trait analysis reveals shared genetic architecture between Alzheimer’s disease and gastrointestinal tract disorders. Communications Biology. 5 (1): ARTN 691.
    Source Title
    Communications Biology
    DOI
    10.1038/s42003-022-03607-2
    ISSN
    2399-3642
    Faculty
    Faculty of Health Sciences
    School
    Curtin School of Population Health
    URI
    http://hdl.handle.net/20.500.11937/97669
    Collection
    • Curtin Research Publications
    Abstract

    Consistent with the concept of the gut-brain phenomenon, observational studies suggest a relationship between Alzheimer’s disease (AD) and gastrointestinal tract (GIT) disorders; however, their underlying mechanisms remain unclear. Here, we analyse several genome-wide association studies (GWAS) summary statistics (N = 34,652–456,327), to assess the relationship of AD with GIT disorders. Findings reveal a positive significant genetic overlap and correlation between AD and gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), gastritis-duodenitis, irritable bowel syndrome and diverticulosis, but not inflammatory bowel disease. Cross-trait meta-analysis identifies several loci (Pmeta-analysis < 5 × 10−8) shared by AD and GIT disorders (GERD and PUD) including PDE4B, BRINP3, ATG16L1, SEMA3F, HLA-DRA, SCARA3, MTSS2, PHB, and TOMM40. Colocalization and gene-based analyses reinforce these loci. Pathway-based analyses demonstrate significant enrichment of lipid metabolism, autoimmunity, lipase inhibitors, PD-1 signalling, and statin mechanisms, among others, for AD and GIT traits. Our findings provide genetic insights into the gut-brain relationship, implicating shared but non-causal genetic susceptibility of GIT disorders with AD’s risk. Genes and biological pathways identified are potential targets for further investigation in AD, GIT disorders, and their comorbidity.

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