Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
Laboratory of Data Discovery for Health (D24H), Hong Kong Science Park, Pak Shek Kok, Hong Kong.
J Med Virol. 2022 Oct;94(10):4735-4743. doi: 10.1002/jmv.27920. Epub 2022 Jun 20.
This study aimed to evaluate the host genetic liability of coronavirus disease 2019 (covid-19) with platelet traits using the Mendelian randomization (MR) approach. We conducted a bidirectional two-sample MR using summary statistics from the largest genome-wide association study of three variables, covid-19 severity (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection, covid-19 hospitalization, and severe covid-19, N = ~1 059 456-1 557 411) and four platelet traits (mean platelet volume [MPV], plateletcrit, platelet distribution width, and platelet count; N = 408 112). Inverse-variance weighted (IVW), median weighted, MR-Egger, and contamination mixture methods were used to estimate the causal association. Null and inconsistent associations in the IVW and sensitivity analyses were observed for SARS-CoV-2 infection and covid-19 hospitalization with platelet traits. For severe covid-19, significant associations with MPV and platelet count were observed in the IVW and sensitivity analyses, with the beta of 0.01 (95% confidence interval [CI]: 0.005-0.016, p = 3.51 × 10 ) and -0.009 (95% CI: -0.015 to -0.002, p = 0.008) per doubling in odds of severe covid-19, respectively. Conversely, null associations were observed for platelet traits with covid-19 traits. In conclusion, host genetic liability to severe covid-19 was causally associated with increased MPV and reduced platelet count, which may provide insights into evaluating hypercoagulability and thromboembolic events in covid-19 patients.
本研究旨在采用孟德尔随机化（MR）方法，利用血小板特征评估 2019 年冠状病毒病（COVID-19）的宿主遗传易感性。我们使用最大的全基因组关联研究中三个变量（COVID-19 严重程度（SARS-CoV-2 感染、COVID-19 住院和重症 COVID-19）和四个血小板特征（平均血小板体积[MPV]、血小板压积、血小板分布宽度和血小板计数）的汇总统计数据进行了双向两样本 MR。采用逆方差加权（IVW）、中位数加权、MR-Egger 和混杂混合物方法来估计因果关联。对于 SARS-CoV-2 感染和 COVID-19 住院与血小板特征，在 IVW 和敏感性分析中观察到了无效和不一致的关联。对于重症 COVID-19，在 IVW 和敏感性分析中观察到了与 MPV 和血小板计数的显著关联，OR 每增加一倍的β值分别为 0.01（95%CI：0.005-0.016，p=3.51×10 -8 ）和-0.009（95%CI：-0.015 至-0.002，p=0.008）。相反，血小板特征与 COVID-19 特征之间的关联无效。总之，严重 COVID-19 的宿主遗传易感性与 MPV 增加和血小板计数减少相关，这可能为评估 COVID-19 患者的高凝状态和血栓栓塞事件提供了新的视角。
