GENETIC INSIGHTS IN ORTHOPAEDICS: SNPS SHAPING HIP GEOMETRY

Lower limb joint morphology, particularly hip geometry, is a critical factor in the development of orthopedic conditions such as developmental dysplasia of the hip (DDH), femoroacetabular impingement (FAI), and osteoarthritis (OA). Understanding the genetic basis of these anatomical variations could improve the prediction and management of these conditions. Single nucleotide polymorphisms (SNPs), genetic variations at single DNA base-pair levels, are known to influence hip morphology and susceptibility to orthopedic pathologies. This study summarizes existing knowledge from genome-wide association studies (GWAS) on SNPs associated with hip morphology. A systematic literature review was conducted following PRISMA guidelines and registered in PROSPERO. SNPs identified through GWAS were categorized into three subgroups: size (e.g., femoral neck length), structure (e.g., cortical thickness), and shape (e.g., alpha angle). Study quality was assessed using the STREGA checklist to ensure reliability. Gene Ontology (GO) analysis was performed using EnrichR to identify biological processes linked to these SNPs. The SNP-associated genes were also cross-referenced with non-hip OA-associated genes across multiple databases. Concurrently, as part of a larger project, we collect genetic material via cheek swabs and imaging data through weight-bearing computed tomography (WBCT) and angioCT for integration into future analyses. DNA is being extracted and stored for sequencing later on. The systematic review identified 436 SNPs associated with hip morphology through GWAS, with minimal overlap among size, structure, and shape. Notably, there is minimal overlap among these categories, highlighting distinct genetic influences. GO analysis highlighted significant involvement of these SNPs in bone and cartilage development, and DNA transcriptional regulation. Moreover, 52 genes linked to non-hip OA were also associated with hip morphology, suggesting shared genetic mechanisms across lower limb joints. However, the lack of SNP data for non-hip joints remains a critical gap for future research. This study establishes a foundation for understanding the genetic determinants of hip morphology and their implications for orthopedic health. Our SNP panel and findings provide a framework for further clinical validation and underscore the potential for early diagnosis and personalized strategies for conditions like OA.