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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

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    Genetic architecture of host proteins interacting with SARS-CoV-2

    Authors: Maik Pietzner; Eleanor Wheeler; Julia Carrasco-Zanini; Johannes Raffler; Nicola D. Kerrison; Erin Oerton; Victoria P.W. Auyeung; Chris Finan; Juan P. Casas; Rachel Ostroff; Steve A. Williams; Gabi Kastenmüller; Markus Ralser; Eric G. Gamazon; Nicholas J. Wareham; Aroon Dinesh Hingorani; Claudia Langenberg

    doi:10.1101/2020.07.01.182709 Date: 2020-07-01 Source: bioRxiv

    Strategies to develop therapeutics for SARS-CoV-2 infection MESHD may be informed by experimental identification of viral-host protein interactions in cellular assays and measurement of host response proteins in COVID-19 MESHD patients. Identification of genetic variants that influence the level or activity of these proteins in the host could enable rapid in silico assessment in human genetic studies of their causal relevance as molecular targets for new or repurposed drugs to treat COVID-19 MESHD. We integrated large-scale genomic and aptamer-based plasma proteomic data from 10,708 individuals to characterize the genetic architecture of 179 host proteins reported to interact with SARS-CoV-2 proteins MESHD or to participate in the host response to COVID-19 MESHD. We identified 220 host DNA sequence variants acting in cis ( MAF HGNC 0.01-49.9%) and explaining 0.3-70.9% of the variance of 97 of these proteins, including 45 with no previously known protein quantitative trait loci (pQTL) and 38 encoding current drug targets. Systematic characterization of pQTLs across the phenome identified protein-drug-disease links, evidence that putative viral interaction partners such as MARK3 HGNC affect immune response, and establish the first link between a recently reported variant for respiratory failure MESHD of COVID-19 MESHD patients at the ABO HGNC locus and hypercoagulation MESHD, i.e. maladaptive host response. Our results accelerate the evaluation and prioritization of new drug development programmes and repurposing of trials to prevent, treat or reduce adverse outcomes. Rapid sharing and dynamic and detailed interrogation of results is facilitated through an interactive webserver (https://omicscience.org/apps/covidpgwas/).

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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