Recent omic studies prioritised several drug targets associated with coronavirus disease 2019 (COVID-19) severity. However, little evidence was provided to systematically estimate the effect of drug targets on COVID-19 severity in multiple ancestries. In this study, we applied Mendelian randomization (MR) and colocalization approaches to understand the putative causal effects of 16,059 transcripts and 1,608 proteins on COVID-19 severity in European and effects of 610 proteins on COVID-19 severity in African ancestry. We further integrated genetics, clinical and literature evidence to prioritised additional drug targets. Additional sensitivity analyses including multi-trait colocalization and phenome-wide MR were conducted to test for MR assumptions.

中文翻译：

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多祖先组学孟德尔随机化揭示了 COVID-19 严重程度的推定药物靶点

最近的组学研究优先考虑了与 2019 年冠状病毒病 (COVID-19) 严重程度相关的几个药物靶点。然而，几乎没有提供证据来系统地估计药物靶点对多个祖先的 COVID-19 严重程度的影响。在这项研究中，我们应用孟德尔随机化 (MR) 和共定位方法来了解 16,059 种转录本和 1,608 种蛋白质对欧洲 COVID-19 严重程度的假定因果影响以及 610 种蛋白质对非洲血统中 COVID-19 严重程度的影响。我们进一步整合遗传学、临床和文献证据来优先考虑其他药物靶点。进行了额外的敏感性分析，包括多性状共定位和全表型 MR，以测试 MR 假设。