Platelet Indices and Blood Pressure: A Multivariable Mendelian Randomization Study

Abstract

Background: Platelet indices are blood-based parameters reflecting the activation of platelets. Previous studies have identified an association between platelet indices and blood pressure (BP). However, the causal inferences are prone to be biased by confounding effects and reverse causation. We performed a Mendelian randomization (MR) study to compare the causal roles between genetically determined platelet indices and BP level. Methods: Single-nucleotide polymorphisms (SNPs) associated with platelet count (PLT), plateletcrit (PCT), mean platelet volume (MPV), platelet distribution width (PDW), and BP at the level of genomewide significance (p < 5 × 10−8 ) in the UK Biobank were used as instrumental variables. In bi-directional univariable MR analyses, Inverse variance-weighted (IVW), MR-Egger, and weighted median methods were used to obtain estimates for the individual causal power. In addition, heterogeneity and sensitivity analysis was performed to examine the pleiotropy of effect estimates. Finally, multivariable MR analyses were undertaken to disentangle the comparative effects of four platelet indices on blood pressure. Results: In the univariable MR analyses, Increased levels of PLT and PCT were associated with higher BP, and PDW was associated with higher DBP alone. In the reverse direction, SBP had a minor influence on PLT and PCT. In multivariable MR analysis, PDW and PLT revealed an independent effect, whereas the association for PCT and MPV was insignificant after co-linear correction. Conclusion: These findings suggest that platelet and BP may affect each other. PDW and PLT are independent platelet indices influencing BP. Increased platelet activation and aggregation may be involved in the pathogenesis of hypertension which may provide insights into evaluating thromboembolic events in people with high BP. The necessity of initiating antiplatelet therapy among hypertension groups need further investigation.

Assessing Genetic Causality of Periodontal Disease and Atrial Fibrillation by Potential Mediators: A Two-Step Mediating Mendelian Randomization Study

“…To minimize the limitations of observational trials (i.e., effects of potential confounders and reverse causation), we perform the bidirectional and replicated MR analysis to evaluate the causation between periodontal disease and AF. Besides, to appraise the link of multiple risk factors with the outcome and explore the mediating effects, the traditional 2-sample MR method was extended [13]. Multivariable MR (MVMR) and two-step MR were applied in this study simultaneously.…”