A catalog of associations between rare coding variants and COVID-19 outcomes.
Journal
medRxiv : the preprint server for health sciences
Titre abrégé: medRxiv
Pays: United States
ID NLM: 101767986
Informations de publication
Date de publication:
27 Feb 2021
27 Feb 2021
Historique:
pubmed:
4
3
2021
medline:
4
3
2021
entrez:
3
3
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33655273
doi: 10.1101/2020.10.28.20221804
pmc: PMC7924298
pii:
doi:
Types de publication
Preprint
Langues
eng
Subventions
Organisme : Medical Research Council
ID : MC_EX_MR/M009203/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_19059
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M009203/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_19025
Pays : United Kingdom
Organisme : NCATS NIH HHS
ID : UL1 TR001873
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_14089
Pays : United Kingdom
Déclaration de conflit d'intérêts
Competing interests J.E.H., J.A.K., A.D., D.S., N.B, A.Y., A.M., R.L., E.M., X.B., D.S., F.S.P.K., J.D.B., C.O’D., A.J.M., D.A.T., A.H.L., J.M., K.W., L.G., S.E.M, H.M.K., L.D., E.S., M.J., S.B., K.S.M, W.J.S., A.R.S., A.E.L., J.M., J.O., L.H., M.N.C., J.G.R., A.B., G.R.A., and M.A.F. are current employees and/or stockholders of Regeneron Genetics Center or Regeneron Pharmaceuticals. X.Z., S.E., J.W.D. are employees of AbbVie and may hold stock in AbbVie. Financial support for this research was provided by AbbVie through the UKB Exome Sequencing Consortium. AbbVie participated in the interpretation of data, review, and approval of the publication. P.N. and M.M.P are employees and stockholders of Alnylam Pharmaceuticals. J.B.R. has served as an advisor to GlaxoSmithKline and Deerfield Capital and these agencies had no role in the design, implementation or interpretation of this study. S.S., E.W., A.C.P., and E.N.S. are employed by Takeda. S.S. holds shares in Takeda and Janssen. The other authors declare no competing interests.
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