Post-traumatic osteoarthritis (PTOA) is a major consequence of joint injury, leading to early-onset osteoarthritis with substantial disability and socioeconomic burden. Unlike degenerative OA, PTOA arises from trauma-related processes, but its genetic and molecular mechanisms remain poorly understood. This project will leverage the unique multi-omics, clinical, and imaging data within UK Biobank to comprehensively investigate the determinants and biological pathways of PTOA.
We will first perform a genome-wide association study (GWAS) to identify genetic variants linked to PTOA risk and compare their overlap and divergence with degenerative OA loci. Using linked health records, we will evaluate clinical and lifestyle factors associated with PTOA development and progression. Next, we will integrate proteomic and metabolomic profiles to identify circulating biomarkers predictive of post-traumatic joint degeneration. MRI-derived imaging features of knee and hip joints will be analysed to quantify structural changes and tissue responses unique to PTOA.
Machine learning models combining genetic, clinical, biochemical, and imaging information will be developed to predict PTOA risk after injury and identify the most informative predictive features. Finally, we will apply bidirectional Mendelian randomization and genetic colocalization to establish causal relationships between molecular traits and PTOA, and to delineate differences from degenerative OA mechanisms.
Overall, this integrative project will define the genetic architecture, molecular signatures, and structural imaging characteristics specific to PTOA. Findings will advance understanding of disease mechanisms, improve post-injury risk stratification, and identify potential therapeutic targets for early intervention.
