Causal Interplay Between Platelet Indices and Rheumatoid Arthritis: Genetic Evidence From Bidirectional Mendelian...

This study is aimed at comprehensively understanding genetically causal associations between some platelet indices (PIs) and rheumatoid arthritis (RA).

Genetic summary statistics for the 4 types of PIs and RA were derived from Neale Lab, FinnGen, and MRC-IEU consortium. Two-sample Mendelian randomization (TSMR) analysis was utilized to infer the bidirectional causality with the implementation of the inverse-variance weighted (IVW), weighted median (WM), weighted mode, and MR-Egger methods. Sensitivity analysis with leave-one-out method was conducted to assess the robustness of the observed causal estimates.

TSMR results indicated that the genetically-determined plateletcrit (PCT) had a causal association with the higher risk of RA (odds ratio [OR] = 1.13, 95% confidence interval [CI]: 1.01, 1.29, p = 0.012) and seropositive RA (OR = 1.03, 95% CI: 1.01, 1.21, p = 0.003). Both WM method and sensitivity analysis supported that the observed causal estimates were reliable. In the reverse MR analysis, genetic susceptibility leading to RA (Beta [se] = -0.012 [0.006], p = 0.037) was causally related to the decrease in mean platelet volume (MPV).

Our study reveals a positive causal association between PCT and the risk of RA, and that genetic susceptibility to RA is causally associated with a reduced MPV. This provides a reference for further studies on the exploration of mechanisms of platelets in the pathogenesis of RA.