It is plausible that variants in the ACE2 and TMPRSS2 genes might contribute to variation in COVID-19 severity and that these could explain why some people become very unwell whereas most do not. Exome sequence data was obtained for 49,953 UK Biobank subjects, of whom 82 had tested positive for SARS-CoV-2 and could be presumed to have severe disease. A weighted burden analysis was carried out using SCOREASSOC to determine whether there were differences between these cases and the other sequenced subjects in the overall burden of rare, damaging variants in ACE2 or TMPRSS2. There were no statistically significant differences in weighted burden scores between cases and controls for either gene. There were no individual DNA sequence variants with a markedly different frequency between cases and controls. Whether there are small effects on severity, or whether there might be rare variants with major effect sizes, would require studies in much larger samples. Genetic variants affecting the structure and function of the ACE2 and TMPRSS2 proteins are not the main explanation for why some people develop severe symptoms in response to infection with SARS-CoV-2. This research was conducted using the UK Biobank Resource.
Hum Hered

中文翻译：

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ACE2 和 TMPRSS2 基因的变异不是英国生物银行受试者中 COVID-19 严重程度的主要决定因素


ACE2和TMPRSS2基因的变异可能会导致 COVID-19 严重程度的变化，这可以解释为什么有些人会变得非常不适，而大多数人却不会。获得了 49,953 名英国生物银行受试者的外显子组序列数据，其中 82 名受试者的 SARS-CoV-2 检测结果呈阳性，可推测患有严重疾病。使用 SCOREASSOC 进行加权负担分析，以确定这些病例与其他测序受试者在ACE2或TMPRSS2罕见、破坏性变异的总体负担方面是否存在差异。任一基因的病例和对照之间的加权负担分数没有统计学上的显着差异。病例和对照之间没有出现频率显着不同的个体 DNA 序列变异。无论是否对严重程度产生较小的影响，或者是否可能存在具有重大影响大小的罕见变异，都需要在更大的样本中进行研究。影响 ACE2 和 TMPRSS2 蛋白结构和功能的基因变异并不是某些人感染 SARS-CoV-2 后出现严重症状的主要解释。这项研究是利用英国生物银行资源进行的。
 赫里德