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    Relationship of Cognition and Alzheimer’s Disease with Gastrointestinal Tract Disorders: A Large-Scale Genetic Overlap and Mendelian Randomisation Analysis

    Access Status
    In process
    Authors
    Adewuyi, Emmanuel
    O’Brien, E.K.
    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 Porter, T. and Laws, S.M. 2022. Relationship of Cognition and Alzheimer’s Disease with Gastrointestinal Tract Disorders: A Large-Scale Genetic Overlap and Mendelian Randomisation Analysis. International Journal of Molecular Sciences. 23 (24): ARTN 16199.
    Source Title
    International Journal of Molecular Sciences
    DOI
    10.3390/ijms232416199
    ISSN
    1661-6596
    Faculty
    Faculty of Health Sciences
    School
    Curtin School of Population Health
    URI
    http://hdl.handle.net/20.500.11937/97667
    Collection
    • Curtin Research Publications
    Abstract

    Emerging observational evidence suggests links between cognitive impairment and a range of gastrointestinal tract (GIT) disorders; however, the mechanisms underlying their relationships remain unclear. Leveraging large-scale genome-wide association studies’ summary statistics, we comprehensively assessed genetic overlap and potential causality of cognitive traits and Alzheimer’s disease (AD) with several GIT disorders. We demonstrate a strong and highly significant inverse global genetic correlation between cognitive traits and GIT disorders—peptic ulcer disease (PUD), gastritis-duodenitis, diverticulosis, irritable bowel syndrome, and gastroesophageal reflux disease (GERD), but not inflammatory bowel disease (IBD). Further analysis detects 35 significant (p < 4.37 × 10−5) bivariate local genetic correlations between cognitive traits, AD, and GIT disorders (including IBD). Mendelian randomisation analysis suggests a risk-decreasing causality of educational attainment, intelligence, and other cognitive traits on PUD and GERD, but not IBD, and a putative association of GERD with cognitive function decline. Gene-based analysis reveals a significant gene-level genetic overlap of cognitive traits with AD and GIT disorders (IBD inclusive, pbinomial-test = 1.18 × 10−3–2.20 × 10−16). Our study supports the protective roles of genetically-influenced educational attainments and other cognitive traits on the risk of GIT disorders and highlights a putative association of GERD with cognitive function decline. Findings from local genetic correlation analysis provide novel insights, indicating that the relationship of IBD with cognitive traits (and AD) will depend largely on their local effects across the genome.

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