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

Autor:	Fernandes B; University of Texas Health Center at Houston., Enduru N, Fernandes B; University of Texas Health Center at Houston., Bahrami S; The University of Texas Health Science Center at Houston., Dai Y; The University of Texas Health Science Center at Houston., Andreassen O; Oslo University Hospital & Institute of Clinical Medicine, University of Oslo., Zhao Z; The University of Texas Health Science Center at Houston.
Jazyk:	angličtina
Zdroj:	Research square [Res Sq] 2023 Sep 28. Date of Electronic Publication: 2023 Sep 28.
DOI:	10.21203/rs.3.rs-3346282/v1
Abstrakt:	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. Competing Interests: Conflicts of interest disclosures OAA is a consultant to Cortechs.ai, and has received speaker’s honoraria from Lundbeck, Janssen and Sunovion. NE, BSF, SB, YD, and ZZ have nothing to disclose.
Databáze:	MEDLINE
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