A Neanderthal OAS1 isoform protects individuals of European ancestry against COVID-19 susceptibility and severity,Nature Medicine

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A Neanderthal OAS1 isoform protects individuals of European ancestry against COVID-19 susceptibility and severity
Nature Medicine ( IF 82.9 ) Pub Date : 2021-02-25 , DOI: 10.1038/s41591-021-01281-1
Sirui Zhou _{1,

2} , Guillaume Butler-Laporte _{1,

2} , Tomoko Nakanishi _{1,

3,

4,

5} , David R Morrison ₁ , Jonathan Afilalo _{1,

2,

6} , Marc Afilalo _{1,

7} , Laetitia Laurent ₁ , Maik Pietzner ₈ , Nicola Kerrison ₈ , Kaiqiong Zhao _{1,

2} , Elsa Brunet-Ratnasingham _{9,

10} , Danielle Henry ₁ , Nofar Kimchi ₁ , Zaman Afrasiabi ₁ , Nardin Rezk ₁ , Meriem Bouab ₁ , Louis Petitjean ₁ , Charlotte Guzman ₁ , Xiaoqing Xue ₁ , Chris Tselios ₁ , Branka Vulesevic ₁ , Olumide Adeleye ₁ , Tala Abdullah ₁ , Noor Almamlouk ₁ , Yiheng Chen _{1,

3} , Michaël Chassé ₉ , Madeleine Durand ₉ , Clare Paterson ₁₁ , Johan Normark ₁₂ , Robert Frithiof ₁₃ , Miklós Lipcsey _{13,

14} , Michael Hultström _{13,

15} , Celia M T Greenwood _{1,

2,

16} , Hugo Zeberg ₁₇ , Claudia Langenberg _{8,

18} , Elin Thysell ₁₉ , Michael Pollak _{1,

20} , Vincent Mooser ₃ , Vincenzo Forgetta ₁ , Daniel E Kaufmann _{9,

21} , J Brent Richards _{1,

2,

3,

22}

Affiliation

Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Quebec, Canada.
Department of Human Genetics, McGill University, Montréal, Quebec, Canada.
Kyoto-McGill International Collaborative School in Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Research Fellow, Japan Society for the Promotion of Science, Tokyo, Japan.
Department of Medicine, Division of Cardiology, McGill University, Montréal, Quebec, Canada.
Department of Emergency Medicine, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.
Research Centre of the Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada.
Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montréal, Quebec, Canada.
SomaLogic, Inc., Boulder, CO, USA.
Molecular Infection Medicine Sweden (MIMS) and Wallenberg Center for Molecular Medicine, Department of Clinical Microbiology, Section of Infection and Immunology, Umeå University, Umeå, Sweden.
Anaesthesiology and Intensive Care Medicine, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Hedenstierna Laboratory, CIRRUS, Anaesthesiology and Intensive Care Medicine, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Integrative Physiology, Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Gerald Bronfman Department of Oncology, McGill University, Montréal, Quebec, Canada.
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Computational Medicine, Berlin Institute of Health, Charité University Medicine Berlin, Berlin, Germany.
Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
Departments of Medicine and Oncology, McGill University, Montréal, Quebec, Canada.
Department of Medicine, Université de Montréal, Montréal, Quebec, Canada.
Department of Twin Research, King's College London, London, UK.

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 × 10⁻⁸), hospitalization (OR = 0.61, P = 8 × 10⁻⁸) and susceptibility (OR = 0.78, P = 8 × 10⁻⁶). 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.

中文翻译：

尼安德特人 OAS1 亚型可保护欧洲血统的个体免受 COVID-19 的易感性和严重性

为了确定影响 2019 年冠状病毒病 (COVID-19) 易感性和严重性的循环蛋白，我们进行了一项两样本孟德尔随机化 (MR) 研究，快速扫描数百种循环蛋白，同时减少因反向因果关系和混杂导致的偏差。在多达 14,134 例病例和 120 万对照中，我们发现 OAS1 水平的 sd 增加与 COVID-19 死亡或通气减少（优势比 (OR) = 0.54，P = 7 × 10 ^-8）、住院治疗（OR = 0.61，P = 8 × 10 ^-8）和磁化率（OR = 0.78，P = 8 × 10 ^-6）。测量 504 人的 OAS1 水平，我们发现在非感染状态下较高的血浆 OAS1 水平与降低 COVID-19 的易感性和严重性有关。进一步的分析表明，欧洲血统个体中 OAS1 的尼安德特人同种型提供了这种保护。因此，来自 MR 和病例对照研究的证据支持 OAS1 在 COVID-19 不良结果中的保护作用。增加 OAS1 水平的可用药物可以优先用于药物开发。

更新日期：2021-02-25

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