Expanded COVID-19 phenotype definitions reveal distinct patterns of genetic association and protective effects.
Nat Genet
; 54(4): 374-381, 2022 04.
Article
in English
| MEDLINE | ID: covidwho-1784001
ABSTRACT
Multiple COVID-19 genome-wide association studies (GWASs) have identified reproducible genetic associations indicating that there is a genetic component to susceptibility and severity risk. To complement these studies, we collected deep coronavirus disease 2019 (COVID-19) phenotype data from a survey of 736,723 AncestryDNA research participants. With these data, we defined eight phenotypes related to COVID-19 outcomes:
four phenotypes that align with previously studied COVID-19 definitions and four 'expanded' phenotypes that focus on susceptibility given exposure, mild clinical manifestations and an aggregate score of symptom severity. We performed a replication analysis of 12 previously reported COVID-19 genetic associations with all eight phenotypes in a trans-ancestry meta-analysis of AncestryDNA research participants. In this analysis, we show distinct patterns of association at the 12 loci with the eight outcomes that we assessed. We also performed a genome-wide discovery analysis of all eight phenotypes, which did not yield new genome-wide significant loci but did suggest that three of the four 'expanded' COVID-19 phenotypes have enhanced power to capture protective genetic associations relative to the previously studied phenotypes. Thus, we conclude that continued large-scale ascertainment of deep COVID-19 phenotype data would likely represent a boon for COVID-19 therapeutic target identification.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Genome-Wide Association Study
/
COVID-19
Type of study:
Experimental Studies
/
Observational study
/
Prognostic study
/
Reviews
Limits:
Humans
Language:
English
Journal:
Nat Genet
Journal subject:
Genetics, Medical
Year:
2022
Document Type:
Article
Affiliation country:
S41588-022-01042-x
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