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Pietzner, M.* ; Wheeler, E.* ; Carrasco-Zanini, J.* ; Raffler, J. ; Kerrison, N.D.* ; Oerton, E.* ; Auyeung, V.P.W.* ; Luan, J.* ; Finan, C.* ; Casas, J.P.* ; Ostroff, R.* ; Williams, S.A.* ; Kastenmüller, G. ; Ralser, M.* ; Gamazon, E.R.* ; Wareham, N.J.* ; Hingorani, A.D.* ; Langenberg, C.*

Genetic architecture of host proteins involved in SARS-CoV-2 infection.

Nat. Commun. 11:6397 (2020)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Understanding the genetic architecture of host proteins interacting with SARS-CoV-2 or mediating the maladaptive host response to COVID-19 can help to identify new or repurpose existing drugs targeting those proteins. We present a genetic discovery study of 179 such host proteins among 10,708 individuals using an aptamer-based technique. We identify 220 host DNA sequence variants acting in cis (MAF 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 and evidence that putative viral interaction partners such as MARK3 affect immune 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 detailed interrogation of results is facilitated through an interactive webserver (https://omicscience.org/apps/covidpgwas/).
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Association; Disease; Metaanalysis; Reveals; Traits; Target; Risk
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 11, Issue: 1, Pages: , Article Number: 6397 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
Grants national "Covid-19 Cardiovascular Disease Flagship Projects"
Cambridge Trust
4-year Wellcome Trust PhD Studentship
Somalogic
University of Cambridge
National Institute on Aging (NIA)
National Institute for Health Research University College London Hospitals Biomedical Research Centre
UCL British Heart Foundation Research Accelerator Award
German Federal Ministry of Education and Research (BMBF)
National Human Genome Research Institute of the National Institutes of Health
Wellcome Trust
UK Medical Research Council
Francis Crick Institute from Cancer Research UK
Medical Research Council