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

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 indivi...

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Veröffentlicht in:Nature communications Jg. 11; H. 1; S. 6397 - 14
Hauptverfasser: Pietzner, Maik, Wheeler, Eleanor, Carrasco-Zanini, Julia, Raffler, Johannes, Kerrison, Nicola D., Oerton, Erin, Auyeung, Victoria P. W., Luan, Jian’an, Finan, Chris, Casas, Juan P., Ostroff, Rachel, Williams, Steve A., Kastenmüller, Gabi, Ralser, Markus, Gamazon, Eric R., Wareham, Nicholas J., Hingorani, Aroon D., Langenberg, Claudia
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 16.12.2020
Nature Publishing Group
Nature Portfolio
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ABO Blood-Group System - metabolism
Aptamers
Aptamers, Peptide - blood
Aptamers, Peptide - metabolism
Blood Coagulation
Coronaviruses
COVID-19
COVID-19 - genetics
COVID-19 - virology
Deoxyribonucleic acid
DNA
Drug delivery
Drug Delivery Systems
Drug development
Female
Gene Expression Regulation
Gene mapping
Genetic diversity
Genetic variance
Host-Derived Cellular Factors - metabolism
Host-Pathogen Interactions - genetics
Humanities and Social Sciences
Humans
Immune response
Immunosuppressive agents
Internet
Interrogation
Male
Middle Aged
multidisciplinary
Nucleotide sequence
Proteins
Proteins - genetics
Quantitative trait loci
Quantitative Trait Loci - genetics
SARS-CoV-2 - physiology
Science
Science (multidisciplinary)
Severe acute respiratory syndrome coronavirus 2
Therapeutic targets
Viral diseases
ISSN:2041-1723, 2041-1723
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Zusammenfassung: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/ ). Finding effective treatments for COVID-19 depends upon understanding genetic regulation of proteins involved in SARS-CoV-2 infection and host response. Here, the authors identify genetic variants linked to expression of such proteins, data which could lead to the discovery of therapeutic targets.
Bibliographie:ObjectType-Article-1
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-020-19996-z