Weifeng Liao,1,* Xiaoxi Lin,1,* Keyu Liu,2,* Yitian Yang,1,* Lianfang Du,1 Jingjing Pan,1 Feiju Chen,1 Weilong Ye,1 Bainian Chen,1 Riken Chen,1 Wenliang Chen,3,4 Weimin Yao1 

1Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524003, People’s Republic of China; 2Department of Anesthesia, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524003, People’s Republic of China; 3Translational Medicine Center, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524003, People’s Republic of China; 4The Medical Interdisciplinary Science Research Center of Western Guangdong, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524003, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Wenliang Chen; Weimin Yao, Email chenwl@gdmu.edu.cn; 490296443@qq.com

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, p = 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, p = 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.

Keywords: platelet count, plateletcrit, mean platelet volume, platelet distribution width, chronic obstructive pulmonary disease, mendelian randomization