GWAS Data Show Shared Genetics Between Alzheimer’s and GI Tract Disorders

An analysis of summary data from large-scale genome-wide association studies (GWAS) revealed shared genetics between Alzheimer’s disease and gastrointestinal tract disorders. Researchers published their findings online in Communications Biology.

“Consistent with previous conventional observational studies, our findings confirm a risk-increasing relationship between Alzheimer’s disease and gastrointestinal tract disorders and provide insights into their underlying biological mechanisms,” wrote lead and corresponding author Emmanuel O. Adewuyi, PhD, of Edith Cowan University Center for Precision Health in Perth, Australia, and coauthors.

According to the study, the analyses identified positive genetic overlap and correlation between Alzheimer’s disease and gastroesophageal reflux disease, peptic ulcer disease, gastritis-duodenitis, irritable bowel syndrome, and diverticulosis — but not between Alzheimer’s disease and inflammatory bowel disease. Investigators pointed out, however, that inflammatory bowel disease was underpowered compared with data sets for other gastrointestinal disorders in the study and advised continued study as more powerful data become available.

Loci shared by Alzheimer’s disease and gastrointestinal tract disorders included PDE4B, BRINP3, ATG16L1, SEMA3F, HLA-DRA, SCARA3, MTSS2, PHB, and TOMM40, cross-trait meta-analysis revealed. Colocalization and gene-based analyses reinforced the finding.

Biological pathway-based analyses showed significant enrichment of lipid metabolism, autoimmunity, lipase inhibitors, programmed cell death 1 signaling, and statin mechanisms for Alzheimer’s disease and gastrointestinal tract traits, researchers reported.

“Our findings provide genetic insights into the gut-brain relationship, implicating shared but noncausal genetic susceptibility of gastrointestinal tract disorders with Alzheimer’s disease risk,” the authors advised. “Genes and biological pathways identified are potential targets for further investigation in Alzheimer’s disease, gastrointestinal tract disorders, and their comorbidity.”

—Jolynn Tumolo

Reference:
Adewuyi EO, O'Brien EK, Nyholt DR, Porter T, Laws SM. A large-scale genome-wide cross-trait analysis reveals shared genetic architecture between Alzheimer’s disease and gastrointestinal tract disorders. Communications Biology. 2022;5(1):691.