Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, D-04103 Leipzig, Germany;
Department of Neuroscience, Karolinska Institutet, SE-17177 Stockholm, Sweden.
Proc Natl Acad Sci U S A. 2021 Mar 2;118(9). doi: 10.1073/pnas.2026309118.
It was recently shown that the major genetic risk factor associated with becoming severely ill with COVID-19 when infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is inherited from Neandertals. New, larger genetic association studies now allow additional genetic risk factors to be discovered. Using data from the Genetics of Mortality in Critical Care (GenOMICC) consortium, we show that a haplotype at a region on chromosome 12 associated with requiring intensive care when infected with the virus is inherited from Neandertals. This region encodes proteins that activate enzymes that are important during infections with RNA viruses. In contrast to the previously described Neandertal haplotype that increases the risk for severe COVID-19, this Neandertal haplotype is protective against severe disease. It also differs from the risk haplotype in that it has a more moderate effect and occurs at substantial frequencies in all regions of the world outside Africa. Among ancient human genomes in western Eurasia, the frequency of the protective Neandertal haplotype may have increased between 20,000 and 10,000 y ago and again during the past 1,000 y.
最近的研究表明,感染严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)后,与 COVID-19 重症相关的主要遗传风险因素是从尼安德特人那里遗传下来的。新的、更大的遗传关联研究现在允许发现其他遗传风险因素。利用来自重症监护患者死亡率遗传学(GenOMICC)联盟的数据,我们发现,与感染病毒时需要重症监护相关的染色体 12 上的一个单倍型是从尼安德特人那里遗传下来的。该区域编码的蛋白质可以激活在感染 RNA 病毒时非常重要的酶。与之前描述的增加 COVID-19 重症风险的尼安德特人单倍型不同,这种尼安德特人单倍型对严重疾病具有保护作用。与风险单倍型相比,它的影响更为温和,并且在非洲以外的世界所有地区都以相当高的频率发生。在西欧亚古代人类基因组中,保护性的尼安德特人单倍型的频率可能在 2 万到 1 万年前之间增加,并在过去 1000 年再次增加。