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Exploring COVID-19 causal genes through disease-specific Cis-eQTLs

文献类型： 外文期刊

作者： Zhang, Sainan 1 ; Wang, Ping 1 ; Shi, Lei 2 ; Wang, Chao 1 ; Zhu, Zijun 1 ; Qi, Changlu 1 ; Xie, Yubin 5 ; Yuan, Shuofeng 5 ; Cheng, Liang 1 ; Yin, Xin 4 ; Zhang, Xue 2 ;

作者机构： 1.Harbin Med Univ, Coll Bioinformat Sci & Technol, Harbin 150081, Heilongjiang, Peoples R China

2.Harbin Med Univ, NHC Key Lab Mol Probes & Targeted Diag & Therapy, Harbin 150028, Heilongjiang, Peoples R China

3.Chinese Acad Med Sci & Peking Union Med Coll, Inst Basic Med Sci, McKusick Zhang Ctr Genet Med, State Key Lab Med Mol Biol, Beijing 100005, Peoples R China

4.Chinese Acad Agr Sci, State Key Lab Vet Biotechnol, Harbin Vet Res Inst, Harbin 150069, Heilongjiang, Peoples R China

5.Univ Hong Kong, Li Ka Shing Fac Med, Dept Microbiol, Pokfulam, Hong Kong 999077, Peoples R China

6.Univ Hong Kong, State Key Lab Emerging Infect Dis, Li Ka Shing Fac Med, Pokfulam, Hong Kong 999077, Peoples R China

关键词： COVID-19; Expression quantitative trait loci; Summary data -based mendelian randomization; siRNA transfection

期刊名称：VIRUS RESEARCH （ 影响因子：5.0； 五年影响因子：4.0 ）

ISSN： 0168-1702

年卷期： 2024 年 342 卷

页码：

收录情况： SCI

摘要： Genome-wide association study (GWAS) analysis has exposed that genetic factors play important roles in COVID19. Whereas a deeper understanding of the underlying mechanism of COVID-19 was hindered by the lack of expression of quantitative trait loci (eQTL) data specific for disease. To this end, we identified COVID-19-specific cis-eQTLs by integrating nucleotide sequence variations and RNA-Seq data from COVID-19 samples. These identified eQTLs have different regulatory effect on genes between patients and controls, indicating that SARSCoV-2 infection may cause alterations in the human body's internal environment. Individuals with the TT genotype in the rs1128320 region seemed more susceptible to SARS-CoV-2 infection and developed into severe COVID-19 due to the abnormal expression of IFITM1. We subsequently discovered potential causal genes, of the result, a total of 48 genes from six tissues were identified. siRNA-mediated depletion assays in SARS-CoV-2 infection proved that 14 causal genes were directly associated with SARS-CoV-2 infection. These results enriched existing research on COVID-19 causal genes and provided a new sight in the mechanism exploration for COVID-19.

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