Causal Interplay Between Platelet Indices and Rheumatoid Arthritis: Genetic Evidence From Bidirectional Mendelian Randomization
Objectives This study is aimed at comprehensively understanding genetically causal associations between some platelet indices (PIs) and rheumatoid arthritis (RA). Methods 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. Results 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). Conclusions 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.