He Jiahao, Jiang Qian, Yao Yiting, Shen Yi, Li Juan, Yang Jianuo, Ma Ran, Zhang Nuofu, Liu Chunli
State Key Laboratory of Respiratory Disease, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Front Cardiovasc Med. 2022 Jul 8;9:919640. doi: 10.3389/fcvm.2022.919640. eCollection 2022.
Previous studies have shown that various cell indices are associated with a higher risk of venous thromboembolism (VTE), however, whether these findings reflect a causal relationship remains unclear. Therefore, we performed a two-sample Mendelian randomization (MR) analysis to assess the causal association of various blood cells with VTE risk.
Summary statistics of genetic instruments representing cell indices for erythrocytes, leukocytes, and platelets were extracted from genome-wide association studies of European ancestry, by Two-Sample Mendelian Randomization. Inverse variance weighting (IVW) was used as the primary analytical method for MR. Sensitivity analyses were performed to detect horizontal pleiotropy and heterogeneity.
Genetically predicted red blood cell distribution width, mean reticulocyte volume, and mean red blood cell volume were positively associated with VTE, with odds ratio (OR) of 1.002 [CI 1.000-1.003, = 0.022), 1.003 (CI 1.001-1.004, = 0.001, respectively)] and 1.001 (CI 1.000-1.002, = 0.005). Genetically predicted monocyte count was negatively correlated with VTE, with OR = 0.998 (CI 0.996-0.999, = 0.041).
Genetically liability to high- red blood cell distribution width, mean reticulocyte volume, mean red blood cell volume, and low monocyte count are associated with the higher risk of VTE. Targeting these factors might be a potential strategy to prevent VTE.
既往研究表明，多种细胞指标与静脉血栓栓塞症（VTE）风险较高相关，但这些发现是否反映因果关系仍不明确。因此，我们进行了一项两样本孟德尔随机化（MR）分析，以评估各种血细胞与VTE风险之间的因果关联。
通过两样本孟德尔随机化，从欧洲血统的全基因组关联研究中提取代表红细胞、白细胞和血小板细胞指标的遗传工具的汇总统计数据。采用逆方差加权（IVW）作为MR的主要分析方法。进行敏感性分析以检测水平多效性和异质性。
遗传预测的红细胞分布宽度、平均网织红细胞体积和平均红细胞体积与VTE呈正相关，比值比（OR）分别为1.002[可信区间（CI）1.000 - 1.003，P = 0.022]、1.003（CI 1.001 - 1.004，P = 0.001）和1.001（CI 1.000 - 1.002，P = 0.005）。遗传预测的单核细胞计数与VTE呈负相关，OR = 0.998（CI 0.996 - 0.999，P = 0.041）。
遗传易感性导致的高红细胞分布宽度、平均网织红细胞体积、平均红细胞体积以及低单核细胞计数与VTE风险较高相关。针对这些因素可能是预防VTE的潜在策略。
