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

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.

SUBMITTER: Fernandes B

PROVIDER: S-EPMC10571609 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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

Fernandes Brisa B Enduru Nitesh N Fernandes Brisa B Bahrami Shahram S Dai Yulin Y Andreassen Ole O Zhao Zhongming Z

Research square 20230928

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 A ...[more]

PMID: 37841839

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Dataset Information

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

Publications

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

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