英国生物库受试者中 ACE2 和 TMPRSS2 基因的变异并非 COVID-19 严重程度的主要决定因素。

IF 1.1 4区 生物学 Q4 GENETICS & HEREDITY Human Heredity Pub Date : 2020-01-01 Epub Date: 2021-03-22 DOI:10.1159/000515200
David Curtis
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引用次数: 0

摘要

ACE2 和 TMPRSS2 基因中的变异可能会导致 COVID-19 严重程度的变化,这些变异可以解释为什么有些人会非常不舒服,而大多数人不会。我们获得了 49953 名英国生物库受试者的外显子组序列数据,其中 82 人的 SARS-CoV-2 检测结果呈阳性,可以推测他们患有严重疾病。利用 SCOREASSOC 进行了加权负担分析,以确定这些病例与其他测序对象在 ACE2 或 TMPRSS2 中罕见破坏性变异的总体负担方面是否存在差异。病例与对照组在这两个基因的加权负担得分上没有明显的统计学差异。病例和对照组之间没有出现频率明显不同的单个 DNA 序列变异。至于是否存在对严重程度的微小影响,或者是否存在具有重大影响的罕见变异,则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原因。这项研究是利用英国生物库资源进行的。
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Variants in ACE2 and TMPRSS2 Genes Are Not Major Determinants of COVID-19 Severity in UK Biobank Subjects.

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.

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来源期刊
Human Heredity
Human Heredity 生物-遗传学
CiteScore
2.50
自引率
0.00%
发文量
12
审稿时长
>12 weeks
期刊介绍: Gathering original research reports and short communications from all over the world, ''Human Heredity'' is devoted to methodological and applied research on the genetics of human populations, association and linkage analysis, genetic mechanisms of disease, and new methods for statistical genetics, for example, analysis of rare variants and results from next generation sequencing. The value of this information to many branches of medicine is shown by the number of citations the journal receives in fields ranging from immunology and hematology to epidemiology and public health planning, and the fact that at least 50% of all ''Human Heredity'' papers are still cited more than 8 years after publication (according to ISI Journal Citation Reports). Special issues on methodological topics (such as ‘Consanguinity and Genomics’ in 2014; ‘Analyzing Rare Variants in Complex Diseases’ in 2012) or reviews of advances in particular fields (‘Genetic Diversity in European Populations: Evolutionary Evidence and Medical Implications’ in 2014; ‘Genes and the Environment in Obesity’ in 2013) are published every year. Renowned experts in the field are invited to contribute to these special issues.
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