tetano
Editor, Senior Moderator
Nat Genet
. 2022 Apr 11.
doi: 10.1038/s41588-022-01042-x. Online ahead of print.
Expanded COVID-19 phenotype definitions reveal distinct patterns of genetic association and protective effects
Genevieve H L Roberts[SUP] #[/SUP][SUP] 1 [/SUP], Raghavendran Partha[SUP] #[/SUP][SUP] 2 [/SUP], Brooke Rhead[SUP] #[/SUP][SUP] 2 [/SUP], Spencer C Knight[SUP] 2 [/SUP], Danny S Park[SUP] 2 [/SUP], Marie V Coignet[SUP] 2 [/SUP], Miao Zhang[SUP] 2 [/SUP], Nathan Berkowitz[SUP] 2 [/SUP], David A Turrisini[SUP] 2 [/SUP], Michael Gaddis[SUP] 2 [/SUP], Shannon R McCurdy[SUP] 2 [/SUP], Milos Pavlovic[SUP] 1 [/SUP], Luong Ruiz[SUP] 2 [/SUP], Chodon Sass[SUP] 1 [/SUP], AncestryDNA Science Team; Asher K Haug Baltzell[SUP] 1 [/SUP], Harendra Guturu[SUP] 2 [/SUP], Ahna R Girshick[SUP] 2 [/SUP], Catherine A Ball[SUP] 2 [/SUP], Eurie L Hong[SUP] 2 [/SUP], Kristin A Rand[SUP] 3 [/SUP]
Affiliations
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.
. 2022 Apr 11.
doi: 10.1038/s41588-022-01042-x. Online ahead of print.
Expanded COVID-19 phenotype definitions reveal distinct patterns of genetic association and protective effects
Genevieve H L Roberts[SUP] #[/SUP][SUP] 1 [/SUP], Raghavendran Partha[SUP] #[/SUP][SUP] 2 [/SUP], Brooke Rhead[SUP] #[/SUP][SUP] 2 [/SUP], Spencer C Knight[SUP] 2 [/SUP], Danny S Park[SUP] 2 [/SUP], Marie V Coignet[SUP] 2 [/SUP], Miao Zhang[SUP] 2 [/SUP], Nathan Berkowitz[SUP] 2 [/SUP], David A Turrisini[SUP] 2 [/SUP], Michael Gaddis[SUP] 2 [/SUP], Shannon R McCurdy[SUP] 2 [/SUP], Milos Pavlovic[SUP] 1 [/SUP], Luong Ruiz[SUP] 2 [/SUP], Chodon Sass[SUP] 1 [/SUP], AncestryDNA Science Team; Asher K Haug Baltzell[SUP] 1 [/SUP], Harendra Guturu[SUP] 2 [/SUP], Ahna R Girshick[SUP] 2 [/SUP], Catherine A Ball[SUP] 2 [/SUP], Eurie L Hong[SUP] 2 [/SUP], Kristin A Rand[SUP] 3 [/SUP]
Affiliations
- PMID: 35410379
- DOI: 10.1038/s41588-022-01042-x
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.