Abstract
Background: Genetic variation may contribute to differences in musculoskeletal phenotypes and recovery, but its value for selecting rehabilitation treatments remains uncertain. This scoping review maps evidence linking genetic variants to musculoskeletal traits, exercise adaptation, pain, and outcomes following regenerative interventions. Methods: PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar were searched for English-language studies published from January 2000 through October 2026. Reporting followed PRISMA-ScR. Human genetic association and intervention studies were charted and synthesized narratively. Mechanistic findings were considered separately from clinical evidence. Sample sizes and quantitative results were summarized where available, distinguishing genotype–phenotype associations, genotype-associated changes over time, and genotype-by-treatment interactions. Results: Studies examined variants in genes related to muscle function, extracellular-matrix organization, growth-factor signaling, inflammation, and pain processing. Findings varied by population, sex, outcome, and intervention. In a resistance-training cohort of 602 adults, ACTN3 genotype explained approximately 2% of strength-gain variation, with an association observed in women but not men. Six platelet-rich plasma reports arose from one cohort of 107 patients and 132 elbows, limiting independent replication. Most findings represented phenotype or outcome associations rather than evidence that genotype modifies treatment benefit relative to a comparator. Conclusions: Current evidence supports further investigation of genetic contributions to rehabilitation-related variability but does not justify routine genotyping to select interventions or prescribe loading, intensity, or recovery intervals. Clinical translation requires independent replication, appropriately controlled genotype-by-treatment analyses, and prospective demonstration of benefit beyond established clinical assessment.