血小板指标与肺动脉高压风险：一项两样本多变量孟德尔随机化研究
Platelet indices and the risk of pulmonary arterial hypertension: a two-sample and multivariable Mendelian randomization study.
作者信息
Li Yinuo, Liu Xi, Hong Qian, Xu Rui
机构信息
First School of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.
Department of Cardiology, Central Hospital Affiliated to Shandong First Medical University, Jinan, China.
出版信息
Front Cardiovasc Med. 2024 Aug 8;11:1395245. doi: 10.3389/fcvm.2024.1395245. eCollection 2024.
BACKGROUND
Recent epidemiological studies have indicated a correlation between platelet indices and pulmonary arterial hypertension (PAH), yet the causality between them remains unclear. To explore the causal relationship between four platelet indices and PAH, with the aim of providing a theoretical basis for clinical prevention and treatment.
METHODS
Single-nucleotide polymorphisms (SNPs) associated with platelet-related traits were selected as exposure factors from published genome-wide association studies (GWAS), including: platelet count (PLT), plateletcrit (PCT), mean platelet volume (MPV), and platelet distribution width (PDW). Summary-level data for PAH were obtained from the FinnGen study (248 cases and 289,117 controls). Two-sample and multivariable Mendelian randomization (MR) analyses were conducted to assess the causal relationship between exposure factors and the risk of outcomes. The inverse variance weighted (IVW) method was utilized as the primary MR analysis approach, supplemented by weighted median, mode-based estimation, MR-Egger regression, and the MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) test to detect and adjust for pleiotropy, ensuring the reliability of the results through sensitivity analysis.
RESULTS
(1) The IVW results from the two-sample MR analysis showed a positive causal association between PLT and the risk of developing PAH [(OR = 1.649, 95%CI: 1.206-2.256, = 0.0017)], with the sensitivity analysis confirming the robustness of the causal relationship. The MR-Egger intercept analysis did not detect potential pleiotropy ( = 0.879). (2) The MVMR results showed no statistically significant causal relationship between these four markers and the risk of developing PAH. After adjusting for collinearity, a direct positive causal association was observed between PLT and the risk of developing PAH (OR = 1.525, 95%CI: 1.063-2.189, = 0.022).
CONCLUSION
The positive correlation between PLT and the risk of PAH suggests that correcting elevated platelet levels may reduce the risk of developing PAH.
背景
近期的流行病学研究表明血小板指标与肺动脉高压（PAH）之间存在相关性，但其因果关系仍不明确。为探讨四种血小板指标与PAH之间的因果关系，旨在为临床预防和治疗提供理论依据。
方法
从已发表的全基因组关联研究（GWAS）中选择与血小板相关性状相关的单核苷酸多态性（SNP）作为暴露因素，包括：血小板计数（PLT）、血小板压积（PCT）、平均血小板体积（MPV）和血小板分布宽度（PDW）。PAH的汇总数据来自芬兰基因研究（248例病例和289,117例对照）。进行两样本和多变量孟德尔随机化（MR）分析，以评估暴露因素与结局风险之间的因果关系。采用逆方差加权（IVW）方法作为主要的MR分析方法，并辅以加权中位数、基于模式的估计、MR-Egger回归和MR多效性残差和离群值（MR-PRESSO）检验来检测和校正多效性，通过敏感性分析确保结果的可靠性。
结果
（1）两样本MR分析的IVW结果显示PLT与发生PAH的风险之间存在正因果关联[（OR = 1.649，95%CI：1.206 - 2.256，P = 0.0017）]，敏感性分析证实了因果关系的稳健性。MR-Egger截距分析未检测到潜在的多效性（P = 0.879）。（2）MVMR结果显示这四种标志物与发生PAH的风险之间无统计学显著的因果关系。校正共线性后，观察到PLT与发生PAH的风险之间存在直接正因果关联（OR = 1.525，95%CI：1.063 - 2.189，P = 0.022）。
结论
PLT与PAH风险之间的正相关表明，纠正血小板水平升高可能降低发生PAH的风险。
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