Association Between Platelet Indices and Risk of Chronic Obstructive Pulmonary Disease: A Bidirectional Mendelian Randomization Study.

Introduction: Platelet indices are associated with chronic obstructive pulmonary disease (COPD), their causal relationship remains unclear. This study aims to explore the causal relationship between four common platelet indices and COPD using Mendelian randomization (MR), including platelet count (PLT), plateletcrit (PCT), mean platelet volume (MPV), and platelet distribution width (PDW).

Methods: We analyzed summary statistics from European-ancestry genome-wide association studies (GWAS) for platelet indices (UK Biobank, n=408,112) and COPD (FinnGen, n=433,208). MR analyses were performed using Inverse Variance Weighting (IVW), MR Egger (ME), Simple Mode (SM), Weighted Median (WMe), and Weighted Mode (WMo). Heterogeneity between SNPs was assessed using Cochran's Q test in combination with a random-effects IVW approach. MR-Egger intercept test and MR-PRESSO analysis demonstrate horizontal pleiotropy. Leave-one-out analysis to assess outlier-driven bias.

Results: IVW analysis indicated that higher PLT was suggestively associated with increased COPD risk (OR = 1.054, 95% CI = 1.005-1.056, = 0.029, FDR = 0.116). In the reverse direction, COPD was suggestively associated with increased PCT (OR = 1.025, 95% CI = 1.003-1.048, = 0.024, FDR= 0.096). No significant associations were observed for MPV or PDW. Sensitivity analyses confirmed the robustness of results, with no signs of pleiotropy or reverse causality.

Conclusion: Our bidirectional MR analysis found no definitive causal relationship between platelet indices and COPD, but observed suggestive associations between higher PLT/PCT and an increased risk of COPD. These findings warrant further investigation into the roles of platelet indices in COPD pathogenesis and their potential as biomarkers or therapeutic targets.