Genetic architecture of host proteins involved in SARS-CoV-2 infection.
Nat Commun
; 11(1): 6397, 2020 12 16.
Article
in English
| MEDLINE | ID: covidwho-1023894
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/ ).
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Proteins
/
Host-Pathogen Interactions
/
SARS-CoV-2
/
COVID-19
Type of study:
Experimental Studies
/
Randomized controlled trials
/
Systematic review/Meta Analysis
Topics:
Variants
Limits:
Female
/
Humans
/
Male
/
Middle aged
Language:
English
Journal:
Nat Commun
Journal subject:
Biology
/
Science
Year:
2020
Document Type:
Article
Affiliation country:
S41467-020-19996-z
Similar
MEDLINE
...
LILACS
LIS