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

Guillaume Butler-Laporte; Gundula Povysil; Jack A Kosmicki; Elizabeth T Cirulli; Theodore Drivas; Simone Furini; Chadi Saad; Axel Schmidt; Pawel Olszewski; Urszula Korotko; Mathieu Quinodoz; Elifnaz Çelik; Kousik Kundu; Klaudia Walter; Junghyun Jung; Amy D Stockwell; Laura G Sloofman; Daniel M Jordan; Ryan C Thompson; Diane Del Valle; Nicole Simons; Esther Cheng; Robert Sebra; Eric E Schadt; Seunghee Kim-Schulze; Sacha Gnjatic; Miriam Merad; Joseph D Buxbaum; Noam D Beckmann; Alexander W Charney; Bartlomiej Przychodzen; Timothy Chang; Tess D Pottinger; Ning Shang; Fabian Brand; Francesca Fava; Francesca Mari; Karolina Chwialkowska; Magdalena Niemira; Szymon Pula; J Kenneth Baillie; Alex Stuckey; Antonio Salas; Xabier Bello; Jacobo Pardo-Seco; Alberto Gómez-Carballa; Irene Rivero-Calle; Federico Martinón-Torres; Andrea Ganna; Konrad J Karczewski; Kumar Veerapen; Mathieu Bourgey; Guillaume Bourque; Robert Jm Eveleigh; Vincenzo Forgetta; David Morrison; David Langlais; Mark Lathrop; Vincent Mooser; Tomoko Nakanishi; Robert Frithiof; Michael Hultström; Miklos Lipcsey; Yanara Marincevic-Zuniga; Jessica Nordlund; Kelly M Schiabor Barrett; William Lee; Alexandre Bolze; Simon White; Stephen Riffle; Francisco Tanudjaja; Efren Sandoval; Iva Neveux; Shaun Dabe; Nicolas Casadei; Susanne Motameny; Manal Alaamery; Salam Massadeh; Nora Aljawini; Mansour S Almutairi; Yaseen M Arabi; Saleh A Alqahtani; Fawz S Al Harthi; Amal Almutairi; Fatima Alqubaishi; Sarah Alotaibi; Albandari Binowayn; Ebtehal A Alsolm; Hadeel El Bardisy; Mohammad Fawzy; Fang Cai; Nicole Soranzo; Adam Butterworth; Daniel H Geschwind; Stephanie Arteaga; Alexis Stephens; Manish J Butte; Paul C Boutros; Takafumi N Yamaguchi; Shu Tao; Stefan Eng; Timothy Sanders; Paul J Tung; Michael E Broudy; Yu Pan; Alfredo Gonzalez; Nikhil Chavan; Ruth Johnson; Bogdan Pasaniuc; Brian Yaspan; Sandra Smieszek; Carlo Rivolta; Stephanie Bibert; Pierre-Yves Bochud; Maciej Dabrowski; Pawel Zawadzki; Mateusz Sypniewski; Elżbieta Kaja; Pajaree Chariyavilaskul; Voraphoj Nilaratanakul; Nattiya Hirankarn; Vorasuk Shotelersuk; Monnat Pongpanich; Chureerat Phokaew; Wanna Chetruengchai; Katsushi Tokunaga; Masaya Sugiyama; Yosuke Kawai; Takanori Hasegawa; Tatsuhiko Naito; Ho Namkoong; Ryuya Edahiro; Akinori Kimura; Seishi Ogawa; Takanori Kanai; Koichi Fukunaga; Yukinori Okada; Seiya Imoto; Satoru Miyano; Serghei Mangul; Malak S Abedalthagafi; Hugo Zeberg; Joseph J Grzymski; Nicole L Washington; Stephan Ossowski; Kerstin U Ludwig; Eva C Schulte; Olaf Riess; Marcin Moniuszko; Miroslaw Kwasniewski; Hamdi Mbarek; Said I Ismail; Anurag Verma; David B Goldstein; Krzysztof Kiryluk; Alessandra Renieri; Manuel A R Ferreira; J Brent Richards; DeCOI Host Genetics Group

doi:10.1371/journal.pgen.1010367

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

Journal article

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

Guillaume Butler-Laporte, Gundula Povysil, Jack A Kosmicki, Elizabeth T Cirulli, Theodore Drivas, Simone Furini, Chadi Saad, Axel Schmidt, Pawel Olszewski, Urszula Korotko, …

PLoS genetics, Vol.18(11), pp.e1010367-e1010367

03/11/2022

DOI: https://doi.org/10.1371/journal.pgen.1010367

PMID: 36327219

Abstract

COVID-19 - genetics

Exome - genetics

Genetic Predisposition to Disease

Genome-Wide Association Study

Humans

SARS-CoV-2 - genetics

Toll-Like Receptor 7 - genetics

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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Title: Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative
Creators - without role: Guillaume Butler-Laporte - McGill University
Gundula Povysil - Columbia University
Jack A Kosmicki - Regeneron
Elizabeth T Cirulli - Helix
Theodore Drivas - Children's Hospital of Philadelphia
Simone Furini - University of Siena
Chadi Saad - Qatar Foundation
Axel Schmidt - University Hospital Bonn
Pawel Olszewski - IMAGENE.ME SA, Bialystok, Poland
Urszula Korotko - Medical University of Białystok
Mathieu Quinodoz - Institute of Molecular and Clinical Ophthalmology Basel
Elifnaz Çelik - Institute of Molecular and Clinical Ophthalmology Basel
Kousik Kundu - University of Cambridge
Klaudia Walter - Wellcome Sanger Institute
Junghyun Jung - University of Southern California
Amy D Stockwell - Genentech
Laura G Sloofman - Icahn School of Medicine at Mount Sinai
Daniel M Jordan - Icahn School of Medicine at Mount Sinai
Ryan C Thompson - Genomics
Diane Del Valle - Icahn School of Medicine at Mount Sinai
Nicole Simons - Icahn School of Medicine at Mount Sinai
Esther Cheng - Icahn School of Medicine at Mount Sinai
Robert Sebra - Icahn School of Medicine at Mount Sinai
Eric E Schadt - Icahn School of Medicine at Mount Sinai
Seunghee Kim-Schulze - Icahn School of Medicine at Mount Sinai
Sacha Gnjatic - Icahn School of Medicine at Mount Sinai
Miriam Merad - Tisch Hospital
Joseph D Buxbaum - Icahn School of Medicine at Mount Sinai
Noam D Beckmann - Tisch Hospital
Alexander W Charney - Icahn School of Medicine at Mount Sinai
Bartlomiej Przychodzen - Vanda Pharmaceuticals
Timothy Chang - University of California, Los Angeles
Tess D Pottinger - Columbia University
Ning Shang - Columbia University
Fabian Brand - University Hospital Bonn
Francesca Fava - University of Siena
Francesca Mari - University of Siena
Karolina Chwialkowska - Centre for Bioinformatics and Data Analysis, Medical University of Bialystok, Bialystok, Poland
Magdalena Niemira - Medical University of Białystok
Szymon Pula - IMAGENE.ME SA, Bialystok, Poland
J Kenneth Baillie - Roslin Institute
Alex Stuckey - Genomics England
Antonio Salas - Instituto de Investigación Sanitaria de Santiago
Xabier Bello - Instituto de Investigación Sanitaria de Santiago
Jacobo Pardo-Seco - Instituto de Investigación Sanitaria de Santiago
Alberto Gómez-Carballa - Instituto de Investigación Sanitaria de Santiago
Irene Rivero-Calle - Instituto de Investigación Sanitaria de Santiago
Federico Martinón-Torres - Instituto de Investigación Sanitaria de Santiago
Andrea Ganna - Institute for Molecular Medicine Finland
Konrad J Karczewski - Broad Institute
Kumar Veerapen - Broad Institute
Mathieu Bourgey - McGill University
Guillaume Bourque - McGill University
Robert Jm Eveleigh - McGill University
Vincenzo Forgetta - Jewish General Hospital
David Morrison - Jewish General Hospital
David Langlais - McGill Genome Centre
Mark Lathrop - McGill Genome Centre
Vincent Mooser - McGill University
Tomoko Nakanishi - Jewish General Hospital
Robert Frithiof - Uppsala University
Michael Hultström - McGill University
Miklos Lipcsey - Uppsala University
Yanara Marincevic-Zuniga - Science for Life Laboratory
Jessica Nordlund - Science for Life Laboratory
Kelly M Schiabor Barrett - Helix
William Lee - Helix
Alexandre Bolze - Helix
Simon White - Helix
Stephen Riffle - Helix
Francisco Tanudjaja - Helix
Efren Sandoval - Helix
Iva Neveux - Desert Research Institute
Shaun Dabe - Renown Health
Nicolas Casadei - University of Tübingen
Susanne Motameny - University of Cologne
Manal Alaamery - King Saud bin Abdulaziz University for Health Sciences
Salam Massadeh - King Saud bin Abdulaziz University for Health Sciences
Nora Aljawini - King Saud bin Abdulaziz University for Health Sciences
Mansour S Almutairi - National Guard Health Affairs
Yaseen M Arabi - King Saud bin Abdulaziz University for Health Sciences
Saleh A Alqahtani - Johns Hopkins University
Fawz S Al Harthi - King Abdulaziz City for Science and Technology
Amal Almutairi - King Abdulaziz City for Science and Technology
Fatima Alqubaishi - King Abdulaziz City for Science and Technology
Sarah Alotaibi - King Abdulaziz City for Science and Technology
Albandari Binowayn - King Abdulaziz City for Science and Technology
Ebtehal A Alsolm - King Abdulaziz City for Science and Technology
Hadeel El Bardisy - King Abdulaziz City for Science and Technology
Mohammad Fawzy - King Abdulaziz City for Science and Technology
Fang Cai - Genentech
Nicole Soranzo - Wellcome Sanger Institute
Adam Butterworth - Wellcome Sanger Institute
Daniel H Geschwind - University of California, Los Angeles
Stephanie Arteaga - University of California, Los Angeles
Alexis Stephens - University of California, Los Angeles
Manish J Butte - University of California, Los Angeles
Paul C Boutros - University of California, Los Angeles
Takafumi N Yamaguchi - University of California, Los Angeles
Shu Tao - University of California, Los Angeles
Stefan Eng - University of California, Los Angeles
Timothy Sanders - University of California, Los Angeles
Paul J Tung - University of California, Los Angeles
Michael E Broudy - University of California, Los Angeles
Yu Pan - University of California, Los Angeles
Alfredo Gonzalez - University of California, Los Angeles
Nikhil Chavan - University of California, Los Angeles
Ruth Johnson - McGill University
Bogdan Pasaniuc - University of California, Los Angeles
Brian Yaspan - Genentech
Sandra Smieszek - Vanda Pharmaceuticals
Carlo Rivolta - University Hospital of Basel
Stephanie Bibert - University of Lausanne
Pierre-Yves Bochud - University of Lausanne
Maciej Dabrowski - MNM Bioscience Inc., Cambridge, Massachusetts, United States of America
Pawel Zawadzki - Faculty
Mateusz Sypniewski - MNM Bioscience Inc., Cambridge, Massachusetts, United States of America
Elżbieta Kaja - Poznan University of Medical Sciences
Pajaree Chariyavilaskul - Chulalongkorn University
Voraphoj Nilaratanakul - Chulalongkorn University
Nattiya Hirankarn - Chulalongkorn University
Vorasuk Shotelersuk - Chulalongkorn University
Monnat Pongpanich - Chulalongkorn University
Chureerat Phokaew - Chulalongkorn University
Wanna Chetruengchai - Chulalongkorn University
Katsushi Tokunaga - Genome Medical Science Project, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan
Masaya Sugiyama - Genome Medical Science Project, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan
Yosuke Kawai - Genome Medical Science Project, National Center for Global Health and Medicine (NCGM), Tokyo, Japan
Takanori Hasegawa - Tokyo Medical and Dental University
Tatsuhiko Naito - RIKEN Center for Integrative Medical Sciences
Ho Namkoong - Keio University
Ryuya Edahiro - Osaka University
Akinori Kimura - Tokyo Medical and Dental University
Seishi Ogawa - Karolinska Institutet
Takanori Kanai - Keio University
Koichi Fukunaga - Keio University
Yukinori Okada - Osaka University
Seiya Imoto - Tokyo University of Science
Satoru Miyano - Tokyo Medical and Dental University
Serghei Mangul - Department of Clinical Pharmacy, School of Pharmacy, University of Southern California, Los Angeles, California, United States of America
Malak S Abedalthagafi - King Abdulaziz City for Science and Technology
Hugo Zeberg - Karolinska Institutet
Joseph J Grzymski - Desert Research Institute
Nicole L Washington - Helix
Stephan Ossowski - Genomics
Kerstin U Ludwig - University of Bonn
Eva C Schulte - Institute of Virology
Olaf Riess - Genomics
Marcin Moniuszko - Department of Allergology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
Miroslaw Kwasniewski - Centre for Bioinformatics and Data Analysis, Medical University of Bialystok, Bialystok, Poland
Hamdi Mbarek - Qatar Foundation
Said I Ismail - Qatar Foundation
Anurag Verma - Corporal Michael Crescenz VA Medical Center, Philadelphia, Pennsylvania, United States of America
David B Goldstein - Columbia University
Krzysztof Kiryluk - Columbia University
Alessandra Renieri - University of Siena
Manuel A R Ferreira - Regeneron
J Brent Richards - 5 Prime Sciences Inc, Montreal, Quebec, Canada
DeCOI Host Genetics Group
Publication Details: PLoS genetics, Vol.18(11), pp.e1010367-e1010367
Grant note: 365825 / CIHR C18281/A29019 / Cancer Research UK U24 CA224319 / NCI NIH HHS 409511 / CIHR RG/13/13/30194 / British Heart Foundation MC_PC_20004 / Medical Research Council 100558 / CIHR UL1 TR001873 / NCATS NIH HHS RG/18/13/33946 / British Heart Foundation CH/12/2/29428 / British Heart Foundation
Identifiers: 9912509608331
Academic Unit: Al Jouf University; King Abdulaziz University; King Abdulaziz City for Science & Technology; Qassim University; King Saud Bin Abdulaziz University for Health Sciences
Language: English
Resource Type: Journal article