Exploration of the causal association between osteoarthritis and ankle-foot diseases: evidence from the Mendelian randomization and colocalization analysis.

OBJECTIVE: To investigate the causal relationships between osteoarthritis (OA) and the development of specific foot and ankle diseases, aiming to clarify their mutual influences and underlying mechanisms, and to provide a more comprehensive understanding of these conditions. METHODS: To investigate these potential causal associations, we conducted a bidirectional Mendelian Randomization (MR) study and colocalization analysis. The study was based on genome-wide association studies (GWAS) summary data, including eight foot and ankle diseases and three types of OA. We applied the inverse variance weighted (IVW) method and IVW with multiplicative random effects to analyze the genetic data, aiming to determine whether there is a causal relationship between OA and foot and ankle diseases. RESULTS: The Mendelian Randomization analysis showed that acquired hallux valgus and hallux rigidus increase the risk of OA, particularly knee OA. Conversely, knee OA elevates the risk of acquired hallux valgus, hallux rigidus, and foot fractures. Hip OA is also linked to a higher risk of acquired flat foot. These findings suggest a bidirectional relationship between OA and foot and ankle diseases. CONCLUSIONS: This study provides evidence of bidirectional causal relationships between OA and certain foot and ankle diseases. These findings enhance our understanding of the pathophysiological connections between these conditions and suggest potential areas for targeted interventions and preventive measures. Future research should focus on confirming these genetic associations and exploring their clinical implications in diverse patient populations.