Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Quebec, Canada.
Nat Med. 2021 Apr;27(4):659-667. doi: 10.1038/s41591-021-01281-1. Epub 2021 Feb 25.
To identify circulating proteins influencing Coronavirus Disease 2019 (COVID-19) susceptibility and severity, we undertook a two-sample Mendelian randomization (MR) study, rapidly scanning hundreds of circulating proteins while reducing bias due to reverse causation and confounding. In up to 14,134 cases and 1.2 million controls, we found that an s.d. increase in OAS1 levels was associated with reduced COVID-19 death or ventilation (odds ratio (OR) = 0.54, P = 7 × 10), hospitalization (OR = 0.61, P = 8 × 10) and susceptibility (OR = 0.78, P = 8 × 10). Measuring OAS1 levels in 504 individuals, we found that higher plasma OAS1 levels in a non-infectious state were associated with reduced COVID-19 susceptibility and severity. Further analyses suggested that a Neanderthal isoform of OAS1 in individuals of European ancestry affords this protection. Thus, evidence from MR and a case-control study support a protective role for OAS1 in COVID-19 adverse outcomes. Available pharmacological agents that increase OAS1 levels could be prioritized for drug development.
为了鉴定影响 2019 年冠状病毒病（COVID-19）易感性和严重程度的循环蛋白，我们进行了两样本孟德尔随机化（MR）研究，快速扫描了数百种循环蛋白，同时减少了由于反向因果关系和混杂引起的偏倚。在多达 14134 例病例和 120 万例对照中，我们发现 OAS1 水平每增加一个标准差，COVID-19 死亡或通气（比值比（OR）=0.54，P=7×10）、住院（OR=0.61，P=8×10）和易感性（OR=0.78，P=8×10）的风险降低。在 504 名个体中测量 OAS1 水平，我们发现非感染状态下较高的血浆 OAS1 水平与 COVID-19 易感性和严重程度降低有关。进一步的分析表明，欧洲血统个体中的一种尼安德特人 OAS1 同工型提供了这种保护。因此，MR 和病例对照研究的证据支持 OAS1 在 COVID-19 不良结局中的保护作用。可增加 OAS1 水平的现有药理学药物可优先考虑用于药物开发。
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