TP9.6 From Genes to Geometry: Shared genetic pathways linking hip morphology and osteoarthritis across joints

Abstract Background Hip morphology is a key determinant in the development of hip-related pathology, including femoroacetabular impingement (FAI) and developmental dysplasia of the hip (DDH), and is a major risk factor for early osteoarthritis (OA). While genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) associated with hip geometry, their biological relevance and overlap with OA across different joints remain poorly understood. Purpose To systematically evaluate SNPs associated with hip morphology and investigate shared genetic mechanisms with OA in non-hip joints. Methods A PRISMA-guided systematic review identified GWAS and candidate gene studies reporting SNPs associated with hip morphology. Identified genes were categorized according to morphological domains (size, structure, shape). Gene Ontology (GO) enrichment analysis was performed to identify key biological pathways. Cross-database comparison (GWAS Catalog, OMIM, ClinVar, Ensembl, Phenopedia) was conducted to assess overlap with genes implicated in non-hip OA. Results A total of 49 studies were included, identifying 436 GWAS-derived SNPs associated with hip morphology. Key genes, including SOX9, GDF5, and BMP7, were consistently linked to variations in femoral head shape, acetabular coverage, and structural features relevant to FAI and dysplasia. GO analysis showed enrichment in processes such as skeletal system development, chondrocyte differentiation, and BMP signaling pathways. Notably, 18% of the genes associated with hip morphology overlapped with those implicated in OA of other joints, including the knee. Many SNPs were located in regulatory regions, suggesting they may influence gene expression rather than directly altering protein structure, thereby contributing subtle but cumulative effects on hip development. Despite the large number of associations identified, replication of these variants across studies was limited. Conclusion Hip morphology, and by extension susceptibility to FAI and dysplasia, appears to be influenced by complex polygenic mechanisms. The observed genetic overlap with OA across joints supports the concept that structural predisposition to degeneration may be partly genetically determined. These findings provide a biological framework linking morphology and disease, with potential implications for early risk stratification, patient-specific decision-making, and future preventive strategies in hip preservation surgery.