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Butler-Laporte, G.* ; Povysil, G.* ; Kosmicki, J.A.* ; Cirulli, E.T.* ; Drivas, T.* ; Furini, S.* ; Saad, C.* ; Schmidt, A.* ; Olszewski, P.K.* ; Korotko, U.* ; Quinodoz, M.* ; Çelik, E.* ; Kundu, K.* ; Walter, K.* ; Jung, J.* ; Stockwell, A.D.* ; Sloofman, L.G.* ; Jordan, D.M.* ; Thompson, R.C.* ; Del Valle, D.* ; Simons, N.* ; Cheng, E.* ; Sebra, R.* ; Schadt, E.E.* ; Kim-Schulze, S.* ; Gnjatic, S.* ; Merad, M.* ; Buxbaum, J.D.* ; Beckmann, N.D.* ; Charney, A.W.* ; Przychodzen, B.* ; Chang, T.* ; Pottinger, T.D.* ; Shang, N.* ; Brand, F.* ; Fava, F.* ; Mari, F.* ; Chwialkowska, K.* ; Niemira, M.* ; Pula, S.* ; Baillie, J.K.* ; Stuckey, A.* ; Salas, A.* ; Bello, X.* ; Pardo-Seco, J.* ; Gómez-Carballa, A.* ; Rivero-Calle, I.* ; Martinón-Torres, F.* ; Ganna, A.* ; Karczewski, K.J.* ; Veerapen, K.* ; Bourgey, M.* ; Bourque, G.* ; Eveleigh, R.J.* ; Forgetta, V.* ; Morrison, D.* ; Langlais, D.* ; Lathrop, M.* ; Mooser, V.* ; Nakanishi, T.* ; Frithiof, R.* ; Hultström, M.* ; Lipcsey, M.* ; Marincevic-Zuniga, Y.* ; Nordlund, J.* ; Schiabor Barrett, K.M.* ; Lee, W.* ; Bolze, A.* ; White, S.* ; Riffle, S.* ; Tanudjaja, F.* ; Sandoval, E.* ; Neveux, I.* ; Dabe, S.* ; Casadei, N.* ; Motameny, S.* ; Alaamery, M.* ; Massadeh, S.* ; Aljawini, N.* ; Almutairi, M.S.* ; Arabi, Y.M.* ; Alqahtani, S.A.* ; Al Harthi, F.S.* ; Almutairi, A.* ; Alqubaishi, F.* ; Alotaibi, S.* ; Binowayn, A.* ; Alsolm, E.A.* ; El Bardisy, H.* ; Fawzy, M.* ; Cai, F.* ; Soranzo, N.* ; Butterworth, A.* ; 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, D.H.* ; Arteaga, S.* ; Stephens, A.E.* ; Butte, M.J.* ; Boutros, P.C.* ; Yamaguchi, T.N.* ; Tao, S.* ; Eng, S.* ; Sanders, T.* ; Tung, P.J.* ; Broudy, M.E.* ; Pan, Y.* ; González, A.J.* ; Chavan, N.* ; Johnson, R.* ; Pasaniuc, B.* ; Yaspan, B.L.* ; Smieszek, S.* ; Rivolta, C.* ; Bibert, S.* ; Bochud, P.Y.* ; Dabrowski, M.* ; Zawadzki, P.* ; Sypniewski, M.* ; Kaja, E.* ; Chariyavilaskul, P.* ; Nilaratanakul, V.* ; Hirankarn, N.* ; Shotelersuk, V.* ; Pongpanich, M.* ; Phokaew, C.* ; Chetruengchai, W.* ; Tokunaga, K.* ; Sugiyama, M.* ; Kawai, Y.* ; Hasegawa, T.* ; Naito, T.* ; Namkoong, H.* ; Edahiro, R.* ; Kimura, A.* ; Ogawa, S.* ; Kanai, T.* ; Fukunaga, K.* ; Imoto, S.* ; Miyano, S.* ; Mangul, S.* ; Abedalthagafi, M.S.* ; Zeberg, H.* ; Grzymski, J.J.* ; Washington, N.L.* ; Ossowski, S.* ; Ludwig, K.U.* ; Schulte, E.C. ; Riess, O.* ; Moniuszko, M.* ; Kwasniewski, M.* ; Mbarek, H.* ; Ismail, S.I.* ; Verma, A.* ; Goldstein, D.B.* ; Kiryluk, K.* ; Renieri, A.* ; Richards, J.B.*

Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative.

PLoS Genet. 18:e1010367 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Proteins
ISSN (print) / ISBN 1553-7390
e-ISSN 1553-7404
Zeitschrift PLoS Genetics
Quellenangaben Band: 18, Heft: 11, Seiten: , Artikelnummer: e1010367 Supplement: ,
Verlag Public Library of Science (PLoS)
Verlagsort 1160 Battery Street, Ste 100, San Francisco, Ca 94111 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)
Förderungen German Research Foundation (DFG)
Stiftung Universitatsmedizin Essen, Germany
Technical University of Munich, Munich, Germany
BONFOR program of the Medical Faculty, University of Bonn
Emmy-Noether programm of the German Research Foundation (DFG)
State of Saarland
Dr. Rolf M. Schwiete Foundation
Munich Clinician Scientist Programm (MCSP)
DFG
Fonds de Recherche Quebec Sante (FRQS)
BMFB
Swiss National Science Foundation
Leenaards Foundation
Santos-Suarez Foundation
MIUR project "Dipartimenti di Eccellenza 2018-2020"
Intesa San Paolo
Compute Canada
Italian Ministry of University and Research
Instituto de Salud Carlos III (ISCIII)
BMBF
Genome Quebec
Public Health Agency of Canada
Canadian Institutes of Health Research (CIHR)
Lady Davis Institute of the Jewish General Hospital
Canadian Foundation for Innovation
Cancer Research UK
NIH
Canadian Institutes of Health Research
Jewish General Hospital Foundation
NIH Foundation
FRQS Merite Clinical Research Scholarship
Calcul Quebec
CIHR fellowships
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 University
National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH)
National Center for Advancing Translational Sciences
McGill Interdisciplinary Initiative in Infection and Immunity (MI4)
Japan Science and Technology Agency (JST)
National Center for Global Health and Medicine
Agency for Medical Research and Development (AMED)
Polish National Science Centre
Medical Research Agency
Perelman School of Medicine at University of Pennsylvania
National Center for Advancing Translational Sciences of the National Institutes of Health under CTSA
Polish Medical Research Agency (ABM)
European Union
Science for Life Laboratory
Knut and Alice Wallenberg Foundation
UCLA David Geffen School of Medicine -Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research Award Program
Netzwerk-Universitaetsmedizin-COVIM: (NaFoUniMedCovid19)
Carigest
Conselleria de Sanidad de la XUNTA de Galicia
GENVIP-IDIS -2021-2024 (SERGAS-IDIS march 2021)
consorcio Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias
Renown Health Foundation
Japan Agency for Medical Research and Development (AMED)
Swiss National Science Foundation (SNF)
Swedish Research Council
Istituto Buddista Italiano Soka Gakkai
Agencia Gallega para la Gestion del Conocimiento en Salud (ACIS)
Agencia Gallega de Innovacion (GAIN): Grupos con Potencial de Crecimiento
F. Hoffmann-La Roche Ltd
U.S. Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, and Biomedical Advanced Research and Development Authority
Nevada Governor's Office of Economic Development
Renown Health
UK Medical Research Council
Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn University
Healthcare-associated Infection Research Group STAR (Special Task Force for Activating Research), Chulalongkorn University
Grant for Development of New Faculty Staff, Ratchadaphiseksomphot Endowment Fund
Health Systems Research Institute, TSRI Fund
Thailand Research Fund
Ratchadapiseksompotch Fund, Faculty of Medicine,Chulalongkorn University, Bangkok, Thailand
e-ASIA Joint Research Program (e-ASIA JRP)
Health Systems Research Institute
Ratchadapisek Sompoch Endowment Fund, Chulalongkorn University, Bangkok, Thailand
NHS Blood and Transplant
National Institute for Health Research