Integrative GWAS Catalog Analysis of Proxy-Trait Intersection in Sarcopenia-Related Musculoskeletal Aging with Multi-Criteria Evidence Integration.

BACKGROUND: Sarcopenia is a multidimensional musculoskeletal-aging phenotype defined by reduced muscle quantity together with weakness and impaired performance, but public genetic resources rarely capture sarcopenia as a single uniformly labeled phenotype. METHODS: Official National Human Genome Research Institute-European Bioinformatics Institute (NHGRI-EBI) genome-wide association studies (GWAS) Catalog association files archived locally on 15 April 2026 were grouped into muscle-quantity and function-frailty domains. Exact shared rsIDs were identified, assigned to catalog representative/mapped genes, evaluated against exploratory skeletal-muscle transcriptomic context, benchmarked with trait-grouping sensitivity analyses, and ranked with a secondary multi-criteria evidence-integration framework. RESULTS: The muscle-quantity domain contained 1580 unique single-nucleotide polymorphisms (SNPs) and the function-frailty domain contained 383 unique SNPs, with 14 exact rsIDs shared between domains. A trait-file permutation benchmark did not show that this overlap exceeded a catalog-level null expectation (empirical p = 0.514), so the shared set is interpreted as a descriptive, high-specificity candidate intersection rather than statistically enriched sharing. Sensitivity analyses showed that the 14-rsID set was retained after excluding falling/fall and chronic obstructive pulmonary disease (COPD)-related proxy traits, indicating that the primary shared set was driven mainly by grip/low-grip function traits. Exploratory transcriptomic context and evidence integration organized candidates for follow-up but did not validate causal or linkage disequilibrium (LD)-level sharing. CONCLUSIONS: This framework generates candidate hypotheses for sarcopenia-related musculoskeletal aging but does not establish causal, fine-mapped, or statistically enriched genetic sharing.