Differential association of platelet indices in NAFLD/NASH: a Mendelian randomized study.

Abstract

Objective: Platelets play important roles in thrombosis, immunity, and inflammation. Recent studies have shown a relationship between platelet indices and nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). However, the nature and direction of this causal relationship remain controversial. This study used two-sample Mendelian randomization (MR) to elucidate the potential causal relationships.

Methods: Genetic associations of platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) were obtained from the summary statistics of a genome-wide association study from the UK Biobank, those of NAFLD/NASH were sourced from the FinnGen database, and two different genome-wide association meta-analyses. Inverse variance weighting was conducted, with weighted median, Mendelian randomisation-Egger, and Mendelian randomisation Pleiotropy Residual Sum and Outlier methods used as sensitivity analyses. Estimates from the inverse variance weighting method were meta-analyzed. Reverse MR Analysis was conducted using NAFLD data.

Results: Increased genetically predicted PDW levels were consistently associated with increased NAFLD risk from all three sources (OR = 1.08, 95% CI = 1.01-1.15; P = 0.020). Genetically predicted NAFLD was associated with increased MPV (OR = 1.008, 95% CI: 1.005-1.032; P = 0.008). Increased levels of genetically predicted PDW were associated with an increased risk of NASH (OR = 1.603, 95% CI: 1.154-2.228; P = 0.005). Decreased levels of genetically predicted PLT and PCT were associated with an increased risk of NASH (OR = 0.679, 95% CI: 0.487-0.947, P = 0.023; OR = 0.587, 95% CI: 0.408-0.843; P = 0.004).

Conclusion: Our results suggest that fluctuations in platelet indices are important in predicting the onset and progression of NAFLD/NASH.