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?:abstract
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A recent report found that rare predicted loss-of-function (pLOF) variants across 13 candidate genes in TLR3- and IRF7-dependent type I IFN pathways explain up to 3.5% of severe COVID-19 cases. We performed whole-exome or whole-genome sequencing of 1,934 COVID-19 cases (713 with severe and 1,221 with mild disease) and 15,251 ancestry-matched population controls across four independent COVID-19 biobanks. We then tested if rare pLOF variants in these 13 genes were associated with severe COVID-19. We identified only one rare pLOF mutation across these genes amongst 713 cases with severe COVID-19 and observed no enrichment of pLOFs in severe cases compared to population controls or mild COVID-19 cases. We find no evidence of association of rare loss-of-function variants in the proposed 13 candidate genes with severe COVID-19 outcomes.
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?:doi
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10.1101/2020.12.18.20248226
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?:doi
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?:journal
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?:license
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?:pdf_json_files
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document_parses/pdf_json/ae7a1baace8a29d9ace2fa751b757b056510acd0.json; document_parses/pdf_json/0fe9e0cc61d7e6e00dd443f62439fb94b1ca1b4d.json
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document_parses/pmc_json/PMC7781338.xml.json
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?:pmid
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?:sha_id
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?:source
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MedRxiv; Medline; PMC; WHO
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?:title
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Failure to replicate the association of rare loss-of-function variants in type I IFN immunity genes with severe COVID-19
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