Exome-wide association study to identify rare variants influencing COVID-19 outcomes : results from the Host Genetics Initiative
Exome-wide association study to identify rare variants influencing COVID-19 outcomes : results from the Host Genetics Initiative
Simple item page
Full item details
- dc.contributor.author
- Butler-Laporte, Guillaume
- Povysil, Gundula
- Kosmicki, Jack A.
- Cirulli, Elizabeth T.
- Drivas, Theodore
- Furini, Simone
- Saad, Chadi
- Schmidt, Axel
- Olszewski, Pawel
- Korotko, Urszula
- Quinodoz, Mathieu
- Çelik, Elifnaz
- Kundu, Kousik
- Walter, Klaudia
- Jung, Junghyun
- Stockwell, Amy D.
- Sloofman, Laura G.
- Jordan, Daniel M.
- Thompson, Ryan C.
- Del Valle, Diane
- Simons, Nicole
- Cheng, Esther
- Sebra, Robert
- Schadt, Eric E.
- Kim-Schulze, Seunghee
- Gnjatic, Sacha
- Merad, Miriam
- Buxbaum, Joseph D.
- Beckmann, Noam D.
- Charney, Alexander W.
- Przychodzen, Bartlomiej
- Chang, Timothy
- Pottinger, Tess D.
- Shang, Ning
- Brand, Fabian
- Fava, Francesca
- Mari, Francesca
- Chwialkowska, Karolina
- Niemira, Magdalena
- Pula, Szymon
- Baillie, J. Kenneth
- Stuckey, Alex
- Salas, Antonio
- Bello, Xabier
- Pardo-Seco, Jacobo
- Gómez-Carballa, Alberto
- Rivero-Calle, Irene
- Martinón-Torres, Federico
- Ganna, Andrea
- Karczewski, Konrad J.
- Veerapen, Kumar
- Bourgey, Mathieu
- Bourque, Guillaume
- Eveleigh, Robert J. M.
- Forgetta, Vincenzo
- Morrison, David
- Langlais, David
- Lathrop, Mark
- Mooser, Vincent
- Nakanishi, Tomoko
- Frithiof, Robert
- Hultström, Michael
- Lipcsey, Miklos
- Marincevic-Zuniga, Yanara
- Nordlund, Jessica
- Schiabor Barrett, Kelly M.
- Lee, William
- Bolze, Alexandre
- White, Simon
- Riffle, Stephen
- Tanudjaja, Francisco
- Sandoval, Efren
- Neveux, Iva
- Dabe, Shaun
- Casadei, Nicolas
- Motameny, Susanne
- Alaamery, Manal
- Massadeh, Salam
- Aljawini, Nora
- Almutairi, Mansour S.
- Arabi, Yaseen M.
- Alqahtani, Saleh A.
- Al Harthi, Fawz S.
- Almutairi, Amal
- Alqubaishi, Fatima
- Alotaibi, Sarah
- Binowayn, Albandari
- Alsolm, Ebtehal A.
- El Bardisy, Hadeel
- Fawzy, Mohammad
- Cai, Fang
- Soranzo, Nicole
- Butterworth, Adam
- COVID-19 Host Genetics Initiative
- DeCOI Host Genetics Group
- GEN-COVID Multicenter Study (Italy)
- Mount Sinai Clinical Intelligence Center
- GEN-COVID consortium (Spain)
- GenOMICC Consortium
- Japan COVID-19 Task Force
- Regeneron Genetics Center
- Geschwind, Daniel H.
- Arteaga, Stephanie
- Stephens, Alexis
- Butte, Manish J.
- Boutros, Paul C.
- Yamaguchi, Takafumi N.
- Tao, Shu
- Eng, Stefan
- Sanders, Timothy
- Tung, Paul J.
- Broudy, Michael E.
- Pan, Yu
- Gonzalez, Alfredo
- Chavan, Nikhil
- Johnson, Ruth
- Pasaniuc, Bogdan
- Yaspan, Brian
- Smieszek, Sandra
- Rivolta, Carlo
- Bibert, Stephanie
- Bochud, Pierre-Yves
- Dabrowski, Maciej
- Zawadzki, Pawel
- Sypniewski, Mateusz
- Kaja, Elżbieta
- Chariyavilaskul, Pajaree
- Nilaratanakul, Voraphoj
- Hirankarn, Nattiya
- Shotelersuk, Vorasuk
- Pongpanich, Monnat
- Phokaew, Chureerat
- Chetruengchai, Wanna
- Tokunaga, Katsushi
- Sugiyama, Masaya
- Kawai, Yosuke
- Hasegawa, Takanori
- Naito, Tatsuhiko
- Namkoong, Ho
- Edahiro, Ryuya
- Kimura, Akinori
- Ogawa, Seishi
- Kanai, Takanori
- Fukunaga, Koichi
- Okada, Yukinori
- Imoto, Seiya
- Miyano, Satoru
- Mangul, Serghei
- Abedalthagafi, Malak S.
- Zeberg, Hugo
- Grzymski, Joseph J.
- Washington, Nicole L.
- Ossowski, Stephan
- Schulte, Eva C.
- Riess, Olaf
- Moniuszko, Marcin
- Kwasniewski, Miroslaw
- Mbarek, Hamdi
- Ismail, Said I.
- Verma, Anurag
- Goldstein, David B.
- Kiryluk, Krzysztof
- Renieri, Alessandra
- Ferreira, Manuel A. R.
- Richards, J. Brent
- Ludwig, Kerstin U.
- dc.date.accessioned
- 2025-02-05T15:03:11Z
- dc.date.available
- 2025-02-05T15:03:11Z
- dc.date.issued
- 2022-11-03
- dc.description.abstract - en
- Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75-10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.
- dc.description.sponsorship
- Genome sequencing of Biobanque Québec COVID-19 was funded by the CanCOGeN HostSeq project, with contribution from Fonds de Recherche Québec Santé (FRQS), Génome Québec, and the Public Health Agency of Canada. The Richards group is supported by the Canadian Institutes of Health Research (CIHR), the Lady Davis Institute of the Jewish General Hospital, the Canadian Foundation for Innovation, the NIH, Cancer Research UK, and FRQS. The Richards research group is supported by the Canadian Institutes of Health Research (CIHR: 365825; 409511, 100558, 169303), the McGill Interdisciplinary Initiative in Infection and Immunity (MI4), the Lady Davis Institute of the Jewish General Hospital, the Jewish General Hospital Foundation, the Canadian Foundation for Innovation, the NIH Foundation, Cancer Research UK, Genome Québec, the Public Health Agency of Canada, McGill University, Cancer Research UK [grant number C18281/A29019] and the Fonds de Recherche Québec Santé (FRQS). JBR is supported by a FRQS Mérite Clinical Research Scholarship. Support from Calcul Québec and Compute Canada is acknowledged. GBL is supported by FRQS and CIHR fellowships. The Columbia COVID-19 Biobank is supported by the Vagelos College of Physicians & Surgeons Office for Research, Precision Medicine Resource, and Biomedical Informatics Resource of the Columbia University Irving Institute for Clinical and Translational Research (CTSA). Columbia CTSA is funded by the National Center for Advancing Translational Sciences (UL1TR001873). The Columbia University COVID-19 Biobank was supported by Columbia University and the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), through grant no. UL1TR001873. DeCOI NGS was supported by funding from the German Research Foundation (DFG; INST 217/1011-1) and were performed at the DFG-funded NGS Competence Center Tübingen (INST 37/1049-1) – Project-ID 286/2020B01 – 428994620 and the DFG-funded West German Genome Center (INST 216/981-1) - Project Number 407493903. Funding for this work was further received from the Stiftung Universitätsmedizin Essen, Germany. The COMRI cohort is funded through in-house institutional funding of the Technical University of Munich, Munich, Germany. Individual grants are as follows: AS is supported by the BONFOR program of the Medical Faculty, University of Bonn (O-149.0134). KUL is supported by the Emmy-Noether programm of the German Research Foundation (DFG; LU 1944/3-1). RB was supported by the State of Saarland and the Dr. Rolf M. Schwiete Foundation. ECS is supported by the Munich Clinician Scientist Programm (MCSP) and the DFG (SCHU2419/2-1). JR received funding from DFG, RY159/3-1; DFG SFB1403; BMBF COVIM 01KX2021. MA and PS were supported by Netzwerk-Universitaetsmedizin-COVIM: (NaFoUniMedCovid19, FKZ: 01KX2021) and the BMFB (Idepico). For FhOGID: P-YB is supported by the Swiss National Science Foundation (31CA30_196036, 33IC30_179636 and 314730_192616), the Leenaards Foundation, the Santos-Suarez Foundation as well as grants allocated by Carigest. CR is supported by the Swiss National Science Foundation (31CA30_196036, 31003A_176097, and 310030_204285). The GEN-COVID Multicenter Study (Italy) was funded by the MIUR project “Dipartimenti di Eccellenza 2018-2020” to Department of Medical Biotechnologies University of Siena, Italy (Italian D.L. n.18 March 17, 2020), private donors for COVID-19 research, “Bando Ricerca COVID-19 Toscana” project to Azienda Ospedaliero-Universitaria Senese, charity fund 2020 from Intesa San Paolo dedicated to the project N. B/2020/0119 “Identificazione delle basi genetiche determinanti la variabilità clinica della risposta a COVID-19 nella popolazione italiana”, the Italian Ministry of University and Research for funding within the “Bando FISR 2020” in COVID-19 and the Istituto Buddista Italiano Soka Gakkai for funding the project “PAT-COVID: Host genetics and pathogenetic mechanisms of COVID-19” (ID n. 2020-2016_RIC_3). The GEN-COVID (Spain) study received support from Instituto de Salud Carlos III (ISCIII): GePEM (PI16/01478/Cofinanciado FEDER; A.S.), DIAVIR (DTS19/00049/Cofinanciado FEDER, A.S.), Resvi-Omics (PI19/01039/Cofinanciado FEDER, A.S.), ReSVinext (PI16/01569/Cofinanciado FEDER, F.M.T.), Enterogen (PI19/01090/Cofinanciado FEDER, F.M.T.); Agencia Gallega para la Gestión del Conocimiento en Salud (ACIS): BI-BACVIR (PRIS-3, A.S.), and CovidPhy (SA 304 C, A.S.); Agencia Gallega de Innovación (GAIN): Grupos con Potencial de Crecimiento (IN607B 2020/08, A.S.), GEN-COVID (IN845D 2020/23, F.M.T.); Framework Partnership Agreement between the Consellería de Sanidad de la XUNTA de Galicia and GENVIP-IDIS - 2021-2024 (SERGAS-IDIS march 2021); and consorcio Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CB21/06/00103; F.M.T.). For Genentech: The COVACTA study was supported by F. Hoffmann-La Roche Ltd and, in part, by federal funds received from the U.S. Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, and Biomedical Advanced Research and Development Authority, under grant number HHSO100201800036C. For Helix+ and Healthy Nevada Project: Funding was provided to Desert Research Institute (DRI) by the Nevada Governor's Office of Economic Development. Funding was provided to the Renown Institute for Health Innovation by Renown Health and the Renown Health Foundation. Thai Biobank (Host genetic factors in COVID-19 patients in relation to disease susceptibility, disease severity and pharmacogenomics) funding was obtained from the following sources: 1.Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn University (RA(PO) 003/63 and 764002-HE01). 2.Grant for the Healthcare-associated Infection Research Group STAR (Special Task Force for Activating Research), Chulalongkorn University (STF 6100430002-1). 3.Grant for Development of New Faculty Staff, Ratchadaphiseksomphot Endowment Fund (DNS 64_002_30_001_2). 4.The e-ASIA Joint Research Program (e-ASIA JRP) as administered by the National Science and Technology Development Agency. 5.Health Systems Research Institute, TSRI Fund (CU_FRB640001_01_30_10) and Thailand Research Fund (DPG6180001). Further, PC is supported by Ratchadapiseksompotch Fund, Faculty of Medicine,Chulalongkorn University, Bangkok, Thailand, Grant number RA(PO) 003/63. VN is supported by Ratchadapiseksompotch Fund, Faculty of Medicine,Chulalongkorn University, Bangkok, Thailand, Grant number RA(PO) 001/63. NH is supported by The e-ASIA Joint Research Program (e-ASIA JRP) as administered by the National Science and Technology Development Agency. VS is supported by Health Systems Research Institute (64-132) and the Ratchadapisek Sompoch Endowment Fund, Chulalongkorn University (764002-HE01), Bangkok, Thailand. Interval was funded by the NHS Blood and Transplant, the National Institute for Health Research, the UK Medical Research Council, and the British Heart Foundation Japan COVID-19 Task Force acknowledges the contribution of Japan Agency for Medical Research and Development (AMED) and Japan Science and Technology Agency (JST). The Japan NCGM-COVID-19 study was supported in part by Grants-in-Aid for Research from the National Center for Global Health and Medicine (20A2009) and the Agency for Medical Research and Development (AMED) (JP20fk0108416 and JP20fk0108104). MNM Diagnostics (Polish COVID WGS) partially supported by the Polish National Science Centre grant No. SZPITALE-JEDNOIMIENNE/2/2020 and by the Medical Research Agency grant No 2020/ABM /COVID19/0022. The Penn Medicine Biobank is supported by Perelman School of Medicine at University of Pennsylvania, a gift from the Smilow family, and the National Center for Advancing Translational Sciences of the National Institutes of Health under CTSA award number UL1TR001878. The POLCOVID-Genomika study was financially supported by the Polish Medical Research Agency (ABM) grant no. 2020/ABM/COVID19/0001. The Qatar Genome Program and Qatar Biobank are both Research, Development & Innovation entities within Qatar Foundation for Education, Science and Community Development. The Saudi COVID-19 acknowledges the Saudi Ministry of Health and King Abdulaziz City for Science and Technology (KACST). The Swedish Biobank received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 824110 (EASI-Genomics). Sequencing was performed by the National Genomics Infrastructure SNP&SEQ facility, which is supported by Science for Life Laboratory, the Swedish Research Council, and the Knut and Alice Wallenberg Foundation. UCLA acknowledges OCRC, Microsoft COVID Compute Funding, Illumina in-kind donation. We thank the UCLA COVID-19 Oversight Research Committee, Microsoft COVID Compute Funding, Illumina in-kind donation, and UCLA David Geffen School of Medicine - Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research Award Program" for funding for this project under award #20-10 ("COVID-19 Host Genomics Registry at UCLA" PI:Pasaniuc).
- dc.identifier.doi
- https://doi.org/10.1371/journal.pgen.1010367
- dc.identifier.issn
- 1553-7404
- dc.identifier.pubmedID
- 36327219
- dc.identifier.uri
- https://open-science.canada.ca/handle/123456789/3395
- dc.language.iso
- en
- dc.publisher - en
- PLOS
- dc.rights - en
- Creative Commons Attribution 4.0 International (CC BY 4.0)
- dc.rights - fr
- Creative Commons Attribution 4.0 International (CC BY 4.0)
- dc.rights.uri - en
- https://creativecommons.org/licenses/by/4.0/
- dc.rights.uri - fr
- https://creativecommons.org/licenses/by/4.0/deed.fr
- dc.subject - en
- Health
- Coronavirus diseases
- Genetics
- dc.subject - fr
- Santé
- Maladie à coronavirus
- Génétique
- dc.subject.en - en
- Health
- Coronavirus diseases
- Genetics
- dc.subject.fr - fr
- Santé
- Maladie à coronavirus
- Génétique
- dc.title - en
- Exome-wide association study to identify rare variants influencing COVID-19 outcomes : results from the Host Genetics Initiative
- dc.type - en
- Article
- dc.type - fr
- Article
- local.acceptedmanuscript.articlenum
- e1010367
- local.article.journalissue
- 11
- local.article.journaltitle - en
- PLoS Genetics
- local.article.journalvolume
- 18
- local.pagination
- 1-26
- local.peerreview - en
- Yes
- local.peerreview - fr
- Oui
Download(s)
Original bundle
1 - 1 of 1
Name: butler-laporte-exome-wide-association-study-rare-variants-influencing-covid-19-outcomes.pdf
Size: 2.75 MB
Format: PDF
Collection(s)