Overview

• Researchers analyzed genome-wide data from over 500,000 Finnish FinnGen participants and validated results in more than 400,000 UK Biobank adults.
• Forty-five of the 53 frailty-linked variants were novel discoveries absent from existing GWAS catalogs.
• Identified variants affect brain function, immune defense and metabolic pathways while showing limited genetic overlap with dementia and cardiovascular risk.
• Proteomics integration and colocalization analyses supported a causal role for genes including CGREF1, APOE and PPP6C.
• Research will now focus on constructing and validating polygenic risk scores for midlife prediction and exploring interventions to delay frailty onset.