Shared genes between Alzheimer's disease and ischemic stroke

Area of Science:

• Genetics
• Neuroscience
• Immunology

Background:

• Alzheimer's disease (AD) and ischemic stroke (IS) share epidemiological links, but their underlying genetic associations are not well understood.
• Previous genome-wide association studies (GWAS) have not identified shared susceptibility variants between AD and IS.
• Investigating pleiotropic genes may elucidate the shared genetic basis and common pathogenesis of these two neurological conditions.

Purpose of the Study:

• To identify pleiotropic genes shared between Alzheimer's disease (AD) and ischemic stroke (IS).
• To explore the role of these shared genes in the common pathogenesis of AD and IS.
• To provide potential targets for future research into the mechanisms linking AD and IS.

Main Methods:

• Utilized large-scale GWAS summary statistics for AD and IS.
• Performed gene-based analysis using VEGAS2 and Fisher's meta-analysis on overlapping significant genes.
• Conducted gene expression analysis to examine transcriptional alterations of identified pleiotropic genes.

Main Results:

• Identified 16 pleiotropic genes significantly associated with both AD and IS.
• MS4A4A and TREM2, known AD genes, showed altered expression in IS-affected tissues.
• Prioritized genes, including EPHA1, MS4A4A, UBE2L3, and TREM2, are predominantly immune-related, highlighting the immune system's role.

Conclusions:

• Shared genes between AD and IS provide mechanistic insights into their common pathogenesis, largely driven by the immune system.
• The identified pleiotropic genes serve as candidates for further investigation into AD and IS.
• Findings encourage future research to validate these genes and elucidate their molecular mechanisms in AD and IS.