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

Maik Pietzner, Eleanor Wheeler, Julia Carrasco-Zanini, Johannes Raffler, Nicola D. Kerrison, Erin Oerton, Victoria P. W. Auyeung, Jian’an Luan, Chris Finan, Juan P. Casas, Rachel Ostroff, Steve A. Williams, Gabi Kastenmüller, Markus Ralser, Eric R. Gamazon, Nicholas J. Wareham, Aroon D. Hingorani () and Claudia Langenberg ()
Additional contact information
Maik Pietzner: MRC Epidemiology Unit, University of Cambridge
Eleanor Wheeler: MRC Epidemiology Unit, University of Cambridge
Julia Carrasco-Zanini: MRC Epidemiology Unit, University of Cambridge
Johannes Raffler: Institute of Computational Biology, Helmholtz Zentrum München – German Research Center for Environmental Health
Nicola D. Kerrison: MRC Epidemiology Unit, University of Cambridge
Erin Oerton: MRC Epidemiology Unit, University of Cambridge
Victoria P. W. Auyeung: MRC Epidemiology Unit, University of Cambridge
Jian’an Luan: MRC Epidemiology Unit, University of Cambridge
Chris Finan: University College London
Juan P. Casas: Brigham and Women’s Hospital, Harvard Medical School
Rachel Ostroff: SomaLogic, Inc.
Steve A. Williams: SomaLogic, Inc.
Gabi Kastenmüller: Institute of Computational Biology, Helmholtz Zentrum München – German Research Center for Environmental Health
Markus Ralser: The Francis Crick Institute
Eric R. Gamazon: MRC Epidemiology Unit, University of Cambridge
Nicholas J. Wareham: MRC Epidemiology Unit, University of Cambridge
Aroon D. Hingorani: University College London
Claudia Langenberg: MRC Epidemiology Unit, University of Cambridge

Nature Communications, 2020, vol. 11, issue 1, 1-14

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/ ).

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (6)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-19996-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19996-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-19996-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().