A catalog of associations between rare coding variants and COVID-19 outcomes.
J A KosmickiJ E HorowitzN BanerjeeR LancheA MarckettaE MaxwellX BaiD SunJ D BackmanD SharmaH M KangC O'DushlaineA YadavA J MansfieldA H LiK WatanabeL GurskiS E McCarthyA E LockeS KhalidS O'KeeffeJ MbatchouO ChazaraY HuangE KvikstadA O'NeillP NioiM M ParkerS PetrovskiH RunzJ D SzustakowskiQ WangE WongA Cordova-PalomeraE N SmithS SzalmaX ZhengS EsmaeeliJ W DavisY-P LaiX ChenAnne E JusticeJ B LeaderT MirshahiD J CareyA VermaG SirugoM D RitchieD J RaderG PovysilD B GoldsteinK KirylukE Pairo-CastineiraK RawlikD PaskoS WalkerA MeynertA KousathanasL MoutsianasA TenesaM CaulfieldR ScottJ F WilsonJohn Kenneth BaillieG Butler-LaporteT NakanishiM LathropJ B RichardsM JonesS BalasubramanianWilliam J SalernoA R ShuldinerJ MarchiniJ D OvertonL HabeggerM N CantorJeffrey G ReidA BarasG R AbecasisM A FerreiraPublished in: medRxiv : the preprint server for health sciences (2021)
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease-19 (COVID-19), a respiratory illness that can result in hospitalization or death. We investigated associations between rare genetic variants and seven COVID-19 outcomes in 543,213 individuals, including 8,248 with COVID-19. After accounting for multiple testing, we did not identify any clear associations with rare variants either exome-wide or when specifically focusing on (i) 14 interferon pathway genes in which rare deleterious variants have been reported in severe COVID-19 patients; (ii) 167 genes located in COVID-19 GWAS risk loci; or (iii) 32 additional genes of immunologic relevance and/or therapeutic potential. Our analyses indicate there are no significant associations with rare protein-coding variants with detectable effect sizes at our current sample sizes. Analyses will be updated as additional data become available, with results publicly browsable at https://rgc-covid19.regeneron.com .