Document Type

Journal Article

Publication Title

Communications Biology

Publisher

Springer Nature

School

Centre for Precision Health / School of Medical and Health Sciences

RAS ID

44429

Funders

National Health and Medical Research Council

Grant Number

NHMRC Numbers : APP1161706, APP1191535

Comments

Adewuyi, E.O., O’Brien, E.K., Nyholt, D.R. et al. (2022). A large-scale genome-wide cross-trait analysis reveals shared genetic architecture between Alzheimer’s disease and gastrointestinal tract disorders. Communications Biology, 5, 691.

https://doi.org/10.1038/s42003-022-03607-2

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.

DOI

10.1038/s42003-022-03607-2

Creative Commons License

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

Research Themes

Health

Priority Areas

Neuroscience and neurorehabilitation

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