Common variants at 21q22.3 locus influence MX1 and TMPRSS2 gene expression and susceptibility to severe COVID-19.
Common variants at 21q22.3 locus influence MX1 and TMPRSS2 gene expression and susceptibility to severe COVID-19.
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DOI：
10.1016/j.isci.2021.102322
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发表时间：
2021-04-23
期刊：
影响因子：
5.8
通讯作者：
Capasso M
中科院分区：
文献类型：
--
作者：
Andolfo I;Russo R;Lasorsa VA;Cantalupo S;Rosato BE;Bonfiglio F;Frisso G;Abete P;Cassese GM;Servillo G;Esposito G;Gentile I;Piscopo C;Villani R;Fiorentino G;Cerino P;Buonerba C;Pierri B;Zollo M;Iolascon A;Capasso M
2019冠状病毒病（COVID-19）的既定风险因素是高龄，男性和合并症，但它们不能完全解释疾病表现的广泛性。与宿主抗病毒反应有关的遗传因素为其发病机制提供了新的见解。我们利用全基因组关联研究数据对21号染色体进行了深入的遗传分析，其中包括6，406名因COVID-19住院的患者和902，088名来自COVID-19宿主遗传学倡议的欧洲遗传血统的对照者。我们发现TMPRSS 2和MX 1基因附近的5个单核苷酸多态性与严重COVID-19相关。五种单核苷酸多态性（SNP）的次要等位基因与发生严重COVID-19的风险降低和血液中MX 1的高水平表达相关。我们的研究结果表明，宿主遗传因素可以影响COVID-19的不同临床表现，MX 1可能是一个潜在的治疗靶点。对7，970名因COVID-19住院的个体进行了遗传分析TMPRSS 2/MX 1基因座（chr. 21）内的五个SNP与严重COVID-19相关，与血液中MX 1高水平表达相关的五个SNP的次要等位基因MX 1可能是COVID-19患者的潜在治疗靶点遗传学;基因组学
The established risk factors of coronavirus disease 2019 (COVID-19) are advanced age, male sex, and comorbidities, but they do not fully explain the wide spectrum of disease manifestations. Genetic factors implicated in the host antiviral response provide for novel insights into its pathogenesis. We performed an in-depth genetic analysis of chromosome 21 exploiting the genome-wide association study data, including 6,406 individuals hospitalized for COVID-19 and 902,088 controls with European genetic ancestry from the COVID-19 Host Genetics Initiative. We found that five single nucleotide polymorphisms within TMPRSS2 and near MX1 gene show associations with severe COVID-19. The minor alleles of the five single nucleotide polymorphisms (SNPs) correlated with a reduced risk of developing severe COVID-19 and high level of MX1 expression in blood. Our findings demonstrate that host genetic factors can influence the different clinical presentations of COVID-19 and that MX1 could be a potential therapeutic target. Genetic analysis was performed on 7,970 individuals hospitalized for COVID-19 Five SNPs within TMPRSS2/MX1 locus (chr.21) are associated with severe COVID-19 The minor alleles of the five SNPs correlated with high level of MX1 expression in blood MX1 could be a potential therapeutic target in patients with COVID-19 Genetics; Genomics
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遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
影响因子：
5.2
作者：
Benetti, Elisa;Tita, Rossella;Pinto, Anna Maria
通讯作者：
Pinto, Anna Maria
非编码序列变体的功能注释。
影响因子：
48
作者：
Ritchie, Graham R. S.;Dunham, Ian;Zeggini, Eleftheria;Flicek, Paul
通讯作者：
Flicek, Paul
影响因子：
4.5
作者：
Anastassopoulou C;Gkizarioti Z;Patrinos GP;Tsakris A
通讯作者：
Tsakris A
影响因子：
5.4
作者：
Matsuyama, Shutoku;Nagata, Noriyo;Taguchi, Fumihiro
通讯作者：
Taguchi, Fumihiro