SARS-CoV-2 Susceptibility and ACE2 Gene Variations Within Diverse Ethnic Backgrounds.
SARS-CoV-2 Susceptibility and ACE2 Gene Variations Within Diverse Ethnic Backgrounds.
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SARS-COV-2敏感性和ACE2基因变异在不同的种族背景下。
DOI：
10.3389/fgene.2022.888025
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发表时间：
2022
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
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作者：
COVID-19的易感性和进展存在相当大的差异，似乎与年龄、性别、种族和先前存在的健康状况密切相关。然而，据我们所知，缺乏临床弱势群体中COVID-19的队列研究。宿主遗传学也已成为COVID-19的主要风险因素，ACE 2受体的变异（有助于SARS-CoV-2病毒进入细胞）已成为关注的主要焦点。因此，我们询问了英国国民健康服务（NHS）患者的种族多样性队列，以评估ACE 2基因座变异与COVID-19风险之间的关联。我们分析了来自英国100，000基因组计划（100 KGP）的1，837例SARS-CoV-2检测阳性病例和37，207例未检测对照的全基因组测序（WGS）数据，以确定ACE 2编码变体的存在，并提取表达数量性状位点（eQTL）。我们发现了一个剪接位点变异体（rs 2285666）与ACE 2表达增加相关，在SARS-CoV-2阳性患者中相对于100 KGP对照组（p = 0.015），以及在种族内比较中相对于门诊患者住院的欧洲患者中（p = 0.029），ACE 2表达增加。我们还比较了288个eQTL的患病率，其中23个在SARS-CoV-2阳性患者中富集。eQTL rs 12006793具有最大的效应量（d = 0.91），其降低ACE 2表达，并且在对照中更普遍，因此可能降低COVID-19的风险。我们鉴定了三种新的非同义变异体，预测它们会改变ACE 2的功能，并表明这三种变异体（p.K26R、p.H378R、p.Y515N）改变了病毒刺突（S）蛋白的受体亲和力。在欧洲人群中更普遍的变体p.N720D（p < 0.001）可能通过影响ACE 2-TMPRSS 2复合物增加病毒进入。ACE 2基因的遗传变异谱可以为COVID-19患者的风险分层提供信息，并可以部分解释不同种族人群之间疾病易感性和严重程度的差异。
There is considerable variability in the susceptibility and progression for COVID-19 and it appears to be strongly correlated with age, gender, ethnicity and pre-existing health conditions. However, to our knowledge, cohort studies of COVID-19 in clinically vulnerable groups are lacking. Host genetics has also emerged as a major risk factor for COVID-19, and variation in the ACE2 receptor, which facilitates entry of the SARS-CoV-2 virus into the cell, has become a major focus of attention. Thus, we interrogated an ethnically diverse cohort of National Health Service (NHS) patients in the United Kingdom (United Kingdom) to assess the association between variants in the ACE2 locus and COVID-19 risk. We analysed whole-genome sequencing (WGS) data of 1,837 cases who were tested positive for SARS-CoV-2, and 37,207 controls who were not tested, from the UK’s 100,000 Genomes Project (100KGP) for the presence of ACE2 coding variants and extract expression quantitative trait loci (eQTLs). We identified a splice site variant (rs2285666) associated with increased ACE2 expression with an overrepresentation in SARS-CoV-2 positive patients relative to 100KGP controls (p = 0.015), and in hospitalised European patients relative to outpatients in intra-ethnic comparisons (p = 0.029). We also compared the prevalence of 288 eQTLs, of which 23 were enriched in SARS-CoV-2 positive patients. The eQTL rs12006793 had the largest effect size (d = 0.91), which decreases ACE2 expression and is more prevalent in controls, thus potentially reducing the risk of COVID-19. We identified three novel nonsynonymous variants predicted to alter ACE2 function, and showed that three variants (p.K26R, p. H378R, p. Y515N) alter receptor affinity for the viral Spike (S) protein. Variant p. N720D, more prevalent in the European population (p < 0.001), potentially increases viral entry by affecting the ACE2-TMPRSS2 complex. The spectrum of genetic variants in ACE2 may inform risk stratification of COVID-19 patients and could partially explain the differences in disease susceptibility and severity among different ethnic groups.
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影响因子：
64.8
作者：
COVID-19 Host Genetics Initiative
通讯作者：
COVID-19 Host Genetics Initiative
宿主遗传对 COVID-19 严重程度和易感性影响的初步全基因组测序和分析
影响因子：
33.5
作者：
Wang F;Huang S;Gao R;Zhou Y;Lai C;Li Z;Xian W;Qian X;Li Z;Huang Y;Tang Q;Liu P;Chen R;Liu R;Li X;Tong X;Zhou X;Bai Y;Duan G;Zhang T;Xu X;Wang J;Yang H;Liu S;He Q;Jin X;Liu L
通讯作者：
Liu L
影响因子：
5.2
作者：
Benetti, Elisa;Tita, Rossella;Pinto, Anna Maria
通讯作者：
Pinto, Anna Maria
影响因子：
64.8
作者：
Karczewski, Konrad J;Francioli, Laurent C;MacArthur, Daniel G
通讯作者：
MacArthur, Daniel G
DOI：
10.1126/science.abc0870
发表时间：
2020-09-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chan KK;Dorosky D;Sharma P;Abbasi SA;Dye JM;Kranz DM;Herbert AS;Procko E
通讯作者：
Procko E