In a bidirectional two-sample Mendelian randomization and transcriptomic analysis Lin et al. from the Xiangya Hospital, Changsha published in the Journal of Pain Research to investigate the causal relationship between circulating inflammatory proteins and osteoarthritis (OA) using Mendelian randomization and transcriptomic data. The study suggests causal roles for various inflammatory proteins in osteoarthritis pathogenesis. Certain proteins (e.g., interleukin-8, fractalkine) are associated with higher OA risk, while others (e.g., interleukin-10 receptor subunit alpha) correlate with lower risk. Additionally, OA itself may causally influence inflammatory protein levels, particularly in a joint-specific manner (hip vs knee). Six key OA-related inflammation-related genes (IRGs) were identified as potential biomarkers 2).
Critical Review:
This study leverages the strengths of two-sample Mendelian Randomization (MR) to address directionality in inflammation-OA associations, bolstered by transcriptomic analysis. However, several issues warrant scrutiny:
– Causality overreach: While MR reduces confounding, it still relies on assumptions (e.g., no pleiotropy), which are not exhaustively addressed here. The evidence remains “suggestive” rather than definitive.