Shoulder and genetics: what orthopedic surgeons need to know

Common shoulder disorders are a major source of pain and disability worldwide. Although mechanical overload, degeneration, and trauma are well-recognized contributors, substantial variability in disease onset, severity, and response to treatment suggests that biological and inherited factors may also influence disease susceptibility and progression. In recent years, advances in genomic and molecular research have provided new insights into the mechanisms underlying common shoulder pathologies. Evidence from family-based studies, genome-wide association studies, transcriptomic analyses, and causal inference approaches indicates that several common shoulder conditions demonstrate a measurable genetic component. Rotator cuff disease and adhesive capsulitis show the strongest evidence for inherited susceptibility, involving pathways related to extracellular matrix remodeling, inflammation, and fibrosis. Glenohumeral osteoarthritis is primarily characterized by altered gene expression within diseased cartilage and periarticular tissues, although shoulder-specific inherited risk data remain limited. Shoulder instability has been associated with variation in genes involved in collagen synthesis and capsular remodeling, though the distinction between inherited predisposition and secondary molecular responses to injury remains incompletely defined. These findings support the concept that common shoulder pathologies are multifactorial disorders influenced by both genetic susceptibility and disease-specific molecular processes. This narrative review aims to synthesize and contextualize current evidence on the role of genetics in 4 prevalent shoulder conditions: rotator cuff tears, adhesive capsulitis, glenohumeral osteoarthritis, and shoulder instability, with the goal of providing an accessible overview for practicing orthopedic surgeons.