The joint-brain axis: evidence from a Mendelian randomization study of osteoarthritis and cortical structure

Background Osteoarthritis (OA) is a common joint disease that may affect brain function via a joint-brain axis, but its causal impact on brain cortical structures is unclear. Method We used Mendelian randomization (MR), a method that leverages genetic variants as natural experiments, to examine the effects of OA, including knee and hip OA, on cortical surface area (SA) and thickness (TH) of the whole brain and 34 functional regions. We used summary statistics from large-scale genome-wide association studies (GWAS) of OA and brain cortical structures in individuals of European ancestry. Result We found that overall OA was causally associated with reduced SA of the isthmus cingulate (beta: -296.2, 95% CI: -439.1, -153.3, P = 4.82e-05), a brain region involved in mood, memory, and spatial orientation. This suggests that OA may influence neuropsychiatric disorders in OA patients. We also detected several suggestive associations between OA and other brain regions. Conclusion Our study reveals a novel causal link between OA and brain cortical structures, with implications for understanding and treating cognitive impairment and other disorders in OA patients. Our findings also highlight the importance of considering the joint-brain axis in clinical practice and future research.