A large-scale genome-wide cross-trait analysis reveals shared genetic architecture between Alzheimer’s disease and gastrointestinal tract disorders
Citation
Source Title
ISSN
Faculty
School
Collection
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.
Related items
Showing items related by title, author, creator and subject.
-
Adewuyi, Emmanuel (2025)Background/Objectives: Observational studies suggest a link between vascular calcification and dementia or cognitive decline, but the evidence is conflicting, and the underlying mechanisms are unclear. Here, we investigate ...
-
Adewuyi, Emmanuel ; O’Brien, E.K.; Porter, T.; Laws, S.M. (2022)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 ...
-
Melén, E.; Granell, R.; Kogevinas, M.; Strachan, D.; Gonzalez, J.; Wjst, M.; Jarvis, D.; Ege, M.; Braun-Fahrländer, C.; Genuneit, J.; Horak, E.; Bouzigon, E.; Demenais, F.; Kauffmann, F.; Siroux, V.; Michel, S.; von Berg, A.; Heinzmann, A.; Kabesch, M.; Probst-Hensch, N.; Curjuric, I.; Imboden, M.; Rochat, T.; Henderson, J.; Sterne, J.; Mcardle, W.; Hui, J.; James, A.; William Musk, A.; Palmer, L.; Becker, A.; Kozyrskyj, A.; Chan-Young, M.; Park, J.; Leung, A.; Daley, D.; Freidin, M.; Deev, I.; Ogorodova, L.; Puzyrev, V.; Celedón, J.; Brehm, J.; Cloutier, M.; Canino, G.; Acosta-Pérez, E.; Soto-Quiros, M.; Avila, L.; Bergström, A.; Magnusson, J.; Söderhäll, C.; Kull, I.; Scholtens, S.; Marike Boezen, H.; Koppelman, G.; Wijga, A.; Marenholz, I.; Esparza-Gordillo, J.; Lau, Shiew Wei; Lee, Y.; Standl, M.; Tiesler, C.; Flexeder, C.; Heinrich, J.; Myers, R.; Ober, C.; Nicolae, D.; Farrall, M.; Kumar, A.; Moffatt, M.; Cookson, W. (2013)Background: Both asthma and obesity are complex disorders that are influenced by environmental and genetic factors. Shared genetic factors between asthma and obesity have been proposed to partly explain epidemiological ...