Genetic overlap between Alzheimer&apos;s disease and immune-mediated diseases: An atlas of shared genetic determinants and biological convergence

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Abstract

The occurrence of immune disease comorbidities in Alzheimer’s disease (AD) has been observed in both epidemiological and molecular studies, suggesting a neuroinflammatory basis in AD. However, their shared genetic components have not been systematically studied. Here, we composed an atlas of the shared genetic associations between 11 immune-mediated diseases and AD by analyzing genome-wide association studies (GWAS) summary statistics. Our results unveiled a significant genetic overlap between AD and 11 individual immune-mediated diseases despite negligible genetic correlations, suggesting a complex shared genetic architecture distributed across the genome. The shared loci between AD and immune-mediated diseases implicated several genes, including GRAMD1B , FUT2 , ADAMTS4, HBEGF, WNT3, TSPAN14, DHODH, ABCB9 and TNIP1 , all of which are protein-coding genes and thus potential drug targets. Top biological pathways enriched with these identified shared genes were related to the immune system and cell adhesion. In addition, in silico single-cell analyses showed enrichment of immune and brain cells, including neurons and microglia. In summary, our results suggest a genetic relationship between AD and the 11 immune-mediated diseases, pinpointing the existence of a shared however non-causal genetic basis. These identified protein-coding genes have the potential to serve as a novel path to therapeutic interventions for both AD and immune-mediated diseases and their comorbidities.

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Author and article information

Journal

Journal ID (nlm-ta): Res Sq

Journal ID (publisher-id): ResearchSquare

Title: Research Square

Publisher: American Journal Experts

Publication date (Electronic): 28 September 2023

Electronic Location Identifier: rs.3.rs-3346282

Author information

Brisa Fernandes https://orcid.org/0000-0002-3797-7582

Nitesh Enduru https://orcid.org/0000-0002-0255-706X

Yulin Dai https://orcid.org/0000-0003-1874-7893

Ole Andreassen https://orcid.org/0000-0002-4461-3568

Zhongming Zhao https://orcid.org/0000-0002-3477-0914

Article

Other ID: 10.21203/rs.3.rs-3346282

DOI: 10.21203/rs.3.rs-3346282/v1

PMC ID: 10571609

PubMed ID: 37841839

SO-VID: 7d7477b7-2423-4cd0-ae81-e5023dfab92a

License:

This work is licensed under a Creative Commons Attribution 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.