Document Type

Journal Article

Publication Title

International Journal of Molecular Sciences

Volume

23

Issue

24

PubMed ID

36555837

Publisher

MDPI

School

Centre for Precision Health / School of Medical and Health Sciences

RAS ID

52989

Funders

National Health and Medical Research Council

Grant Number

NHMRC Numbers : APP1161706, APP1191535

Comments

Adewuyi, E. O., O’Brien, E. K., Porter, T., & 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), Article 16199.

https://doi.org/10.3390/ijms232416199

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.

DOI

10.3390/ijms232416199

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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