Genetic modifiers of APOE-ε4-associated cognitive decline - PubMed
2 days ago
- #Alzheimer's disease
- #genetics
- #cognitive decline
- The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease but is not deterministic.
- Study conducted cross-ancestry GWAS with 32,778 participants to identify genetic modifiers of APOE-ε4-associated cognitive decline.
- Two genome-wide significant loci in APOE-ε4 carriers were identified, affecting executive function and showing broad cognitive effects.
- In non-carriers, significant associations were found at ITGB8 for executive function and another locus for language.
- Linked loci to genes SEMA6D, GRIN3A, and ITGB8 through expression and methylation databases.
- Post-GWAS analyses implicated additional genes like SLCO1A2 and DNAH11.
- Genetic correlation analyses suggest immune-related traits may exacerbate cognitive risk in APOE-ε4 carriers.