Abstract
BACKGROUND: Osteoarthritis (OA), wherever affecting the hip or knee, is the most commonly diagnosed degenerative joint disorder. However, the relationship between hip osteoarthritis (HOA) and knee osteoarthritis (KOA) remains unclear. Moreover, their specific associations with immune traits also remain unclear. METHOD: Using two-sample Mendelian randomization (MR) analysis, the association between HOA and KOA was comprehensively assessed. To investigate the relationship between immune traits and HOA/KOA, forward MR analysis treated immune traits as the exposure and HOA/KOA as the outcome, Conversely, reverse MR analysis treated HOA/KOA as the exposure and immune phenotypes as the outcome. After adjusting for the false discovery rate, significant statistical associations were identified among KOA and HOA, KOA and immune traits, and HOA and immune traits. RESULTS: The analysis revealed a causal relationship between KOA and HOA, with each increasing the risk of the other. Additionally, several identified immune traits were found to serve as independent factors on KOA and HOA. Specifically, KOA was associated with CD25 on IgD + CD24+, while HOA was associated with CD20 on memory B cells and PDL-1 on CD14- CD16 + monocytes. CONCLUSION: This study provides the first comprehensive evaluation of the interactions between HOA, KOA, and immune responses. These findings offer novel insights into the pathogenesis of HOA and KOA, and suggest potential therapeutic strategies, such as targeting immunological pathways.