Large-scale genome-wide analyses with proteomics integration reveal novel loci and biological insights into frailty.

ABSTRACT: Frailty is a clinically relevant phenotype with notable gaps in our understanding of its etiology. Using the Hospital Frailty Risk Score (HFRS) to define frailty, we performed a genome-wide association study in FinnGen (N = 500,737), replicated the results in the UK Biobank (N = 407,463) and performed a meta-analysis. We prioritized genes through colocalization with expression, splicing and protein quantitative trait loci and proteomics integration. We identified 53 independent lead variants associated with frailty (P < 5 × 10^-8), of which 45 were novel and not previously reported in the GWAS Catalog. Replication at the individual variant and polygenic risk score of the HFRS (P = 1.86 × 10^-522) levels and meta-analysis largely confirmed the findings. Colocalization an

SUBMITTER: Mak JKL 

PROVIDER: S-EPMC12350161 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature