Genetic architecture of host proteins involved in SARS-CoV-2 infection
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Authors
Pietzner, Maik
Carrasco-Zanini, Julia
Kerrison, Nicola D.
Oerton, Erin
Casas, Juan P.
Ostroff, Rachel
Ralser, Markus
Publication Date
2020-12-16Journal Title
Nature Communications
Publisher
Nature Publishing Group UK
Volume
11
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Pietzner, M., Wheeler, E., Carrasco-Zanini, J., Raffler, J., Kerrison, N. D., Oerton, E., Auyeung, V. P. W., et al. (2020). Genetic architecture of host proteins involved in SARS-CoV-2 infection. Nature Communications, 11 (1) https://doi.org/10.1038/s41467-020-19996-z
Description
Funder: Medical Research Council
Abstract
Abstract: 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/).
Keywords
Article, /631/208, /692/53, /45, /45/61, /82/80, article
Identifiers
s41467-020-19996-z, 19996
External DOI: https://doi.org/10.1038/s41467-020-19996-z
This record's URL: https://www.repository.cam.ac.uk/handle/1810/315420
Rights
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/
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