Platelet indices and idiopathic pulmonary fibrosis: a multivariable mendelian randomization study

Abstract

Background The platelet indices can be used to reflect platelet activation. Previous studies have found that platelet activation plays an important role in thrombotic diseases. However, it is still unclear whether platelet activation induces the progression of IPF hypercoagulability. Therefore, we conducted a Mendelian randomization (MR) study to compare the causal relationship between gene determined platelet indices and IPF levels. Methods Single nucleotide polymorphisms (SNPs) were used as instrumental variables in relation to platelet count (PLT), hematocrit (PCT), mean platelet volume (MPV), platelet distribution width (PDW), and blood pressure IPF (p < 5 ×10− 8) from the UK Biobank. In bidirectional univariate MR analysis, inverse variance weighting (IVW), MR Egger, and weighted median methods are applied to obtain estimates of individuals. In addition, heterogeneity and sensitivity analyses were conducted to test the pleiotropy of the effects. Finally, a multivariate MR analysis was conducted to elucidate the comparative effects of the four types of platelets. Results In MR, we found no causal relationship between PLT, MPV, PDW, and PCT levels predicted by host genetics and IPF. In MVMR, the relationship between PLT, MPV, PCT and IPF is significant. Conclusion These findings suggest that PLT, MPV, and PCT as overall features may jointly participate in platelet activation. The increase in platelet activation and aggregation may be involved in the pathogenesis of IPF, which may provide insights for evaluating microvascular thrombosis events in IPF patients.