Genetic overlap between Alzheimer's disease and immune-mediated diseases: an atlas of shared genetic determinants and biological convergence.
Mol Psychiatry
; 2024 Mar 18.
Article
en En
| MEDLINE
| ID: mdl-38499654
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Idioma:
En
Revista:
Mol Psychiatry
Asunto de la revista:
BIOLOGIA MOLECULAR
/
PSIQUIATRIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos