Genetic study of novel coronavirus host | based on GWAS data of 680000 people, IFNAR2 and il10rb genes were found to be associated with the susceptibility of cowid-19

Covid-19 virus is a new type of coronary influenza virus, which is spreading all over the world

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As of December 18, 2020, there are more than 75.89 million confirmed cases and 1.67 million deaths caused by the novel coronavirus

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The pandemic of covid-19 virus is destroying the global economy and health system

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There is an urgent need to understand how to better understand and treat covid-19

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Recently, Professor Su Jianzhong’s team of optometry Hospital Affiliated to Wenzhou Medical University has integrated 680000 people’s GWAS big data to conduct in-depth mining on the susceptibility of new coronavirus (covid-19)

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Relevant research results “integrated genomics and genetics review a 21q22.11 location contributing to us perception of covid-19” was published in the authoritative journal of genetics, human molecular genetics

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Ma Yunlong, associate researcher of the Institute of biological big data, and Huang yukuan, a graduate student, are the co authors

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Prof

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Su Jianzhong and Prof

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Wu Nan are the co corresponding authors

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Previous studies on covid-19 mainly focused on epidemiology, clinical features and viral genomics

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Therefore, more and more researchers pay attention to the host genetic factors leading to the susceptibility of covid-19, which is very necessary to understand the mechanism of virus transmission and develop treatment methods

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In this study, we integrated two independent large sample GWAS data sets (n = 680128), and carried out meta-analysis and multiple bioinformatics joint analysis, including s-multixcan, s-predixcan, magma, Sherlock, drug geneinteraction, gene property, single cell RNA and functional enrichment analysis, to find the host genes related to the susceptibility of cowid-19

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Through meta-analysis, a new locus 21q22.11 (rs9976829 in ifnar2-il10rb gene cluster) was found to be associated with the susceptibility of covid-19

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Recently, our findings were supported by the results published in the journal Nature by pairo castineira et al

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Which indicated that the gene cluster of these two genes was associated with covid-19 infection (pairo-castineira et al

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Genetic polymorphism of critical ill ness virus-19, nature

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2020dec11)

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We further provide evidence at various levels that IFNAR2 and il10rb are involved in covid-19 infection

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The association analysis of SNP mutation level and magma gene level showed that IFNAR2 and il10rb were significantly associated with covid-19

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Individuals with rs9976829g allele were 16% more likely to be infected with cowid-19 than those without G allele (or = 1.16,95% CI = 1.09-1.23)

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Based on the analysis of quantitative trait loci (sqtl) at the cutting sites, rs9976829 was found to represent the sqtl of IFNAR2 and il10rb genes in multiple tissues, especially in lung tissues (P = 1.8) × 10-24)。 Combined with meta GWAS data and eQTL data covering 49 GTEX tissues, two independent integrated genomic analyses were carried out, which showed that gene expression related mutations on IFNAR2 and il10rb had significant effects on covid-19 in multiple tissues (especially lung tissues)

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Subsequently, based on the single cell data of lung tissue, we found that the majority of IFNAR2 expressing cells were dendritic cells (40%) and plasmacytoid dendritic cells (38.5%), while il10rb expressing cells were atypical monocytes (29.6%), indicating that IFNAR2 and il10rb may play a potential regulatory role in lung immune response

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Through drug gene interaction analysis and systematic literature mining, we found that IFNAR2 was targeted by nine FDA approved drugs, including interferon α- N3, interferon α- 1

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And interferon α- Il10rb was targeted by pegylated interferon-lambda-1a

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Recently, two papers published in science provide supporting evidence for the important role of IFN-I deficiency in patients with severe covid-19: IFN-I deficiency in blood may be a marker of severe covid-19 (hadjadjetal

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Science, 2020)

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Congenital defects of type I interferon immunity are associated with life-threatening in non severe patients with cowid-19 (Zhang et al

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Science, 2020)

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In addition, interferon therapy has shown initial efficacy in patients with covid-19, including remission of symptoms and shortening of hospital stay (Huang et al

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Lancet 2020)

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Interferon- β Treatment can effectively block the replication of sars-cov-2 (leietal

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Natural communications, 2020)

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Since there are still a large number of ongoing clinical trials to evaluate the efficacy and safety of interferon products, patients can be grouped according to their IFNAR2 and il10rb alleles to enhance the efficacy and safety of interferon products

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In conclusion, this study revealed that 21q22.11 gene cluster is a new genetic susceptibility site for covid-19, and provided clues for interferons related to IFNAR2 and il10rb genes, which may contribute to the potential treatment of covid-19

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Compared with individuals without G allele, individuals with rs9976829g allele were more likely to be infected with covid-19

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  Index: may #, Huangy #, Zhaos, Yao y, Zhang y, Quj, Wu *, SUJ *

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Integrated genomics and analysis review a 21q22.11 location contributing to us perception of ovid-19.human molecular genetics,   2021May5; ddab125

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  doi:10.1093/hmg/ddab125

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Link to the original text: https://academic.oup.com/hmg/advance-article/doi/10.1093/hmg/ddab125/6265026? login=true。

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