10 research outputs found
Whole-genome sequencing reveals host factors underlying critical COVID-19
- Author
- Abd Elghafar M. S.
- Abdel-Aziz M.
- Abdelrazik M.
- Abdollahi H.
- Abdullah T.
- Abecasis G. R.
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- Wakefield P.
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- Waldron J.
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- Woodford C.
- Woodruff M.
- Woods L.
- Woodyatt W.
- Woolley A. E.
- Worner R.
- Worsley L.
- Wray G.
- Wren L.
- Wright D.
- Wright J.
- Wright M.
- Wrobel N.
- Wu Y.
- Wulandari R.
- Wyllie D. H.
- Wynter I.
- Xavier K.
- Xue X.
- Yadav A.
- Yang J.
- Yassen A. M.
- Yates B.
- Ye C.
- Yun N.
- Zainy T.
- Zak A.
- Zaki A.
- Zamikula J.
- Zanella I.
- Zborowski A. C.
- Zeberg H.
- Zechner M.
- Zguro K.
- Zhang M.
- Zhao J. H.
- Zheng C.
- Zhou W.
- Zitter L.
- Zlatopolsky M.
- Zollner S.
- Zongo O.
- Zucchi P.
- Zyndorf M.
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2022
- Field of study
Get PDFCritical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease
Genetic mechanisms of critical illness in COVID-19.
- Author
- A A Roger Thompson
- A Abraheem
- A Agasou
- A Ahmed
- A Ali
- A Allan
- A Altabaibeh
- A Alvaro
- A Aspinwall
- A Ayers
- A Bamford
- A Barron
- A Bashyal
- A Bellini
- A Bociek
- A Botello
- A Bowes
- A Brady
- A Brayne
- A Brown
- A Brown
- A Butler
- A Campbell
- A Carter
- A Collins
- A Cowley
- A Cowton
- A Cowton
- A Cox
- A Crew
- A Dance
- A Daniel
- A Daniels
- A Dela Rosa
- A Drummond
- A Durie
- A E Heron
- A Easthope
- A Easthope
- A Evans
- A Fofano
- A Gales
- A Ganesan
- A Gardner
- A Garg
- A Gherman
- A Gordon
- A Gratrix
- A Gulati
- A Gupta
- A Haigh
- A Haldeos
- A Harrison
- A Harvey
- A Hayes
- A Higham
- A Higham
- A Hilldrith
- A Holden
- A Hormis
- A Hutcheon
- A Javaid
- A Joseph
- A Kaliappan
- A Katary
- A Kay
- A Kayani
- A Kent
- A Kirkby
- A Knight
- A Kubisz-Pudelko
- A Kuravi
- A Lewis
- A Loveridge
- A Lyle
- A Mayer
- A McAlpine
- A McCarthy
- A McGregor
- A McGregor
- A Meikle
- A Mitchell
- A Mitra
- A Morris
- A Morrison
- A Naranjo
- A Nicholson
- A Nicholson
- A Nilsson
- A Noakes
- A Patel
- A Pickard
- A Poole
- A Price
- A Puxty
- A Quinn
- A Quinn
- A Raithatha
- A Rattray
- A Reddy
- A Reed
- A Reyes
- A Rose
- A Rose
- A Rostron
- A Roy
- A Roynon-Reed
- A S Raj
- A Salberg
- A Sanderson
- A Serrano-Ruiz
- A Solesbury
- A Sukha
- A Swain
- A Tariq
- A Thomas
- A Thomas
- A Todd
- A Tomas
- A Tridente
- A Tucci
- A Turnbull
- A Uriel
- A Ustianowski
- A Vochin
- A Vuylsteke
- A Waite
- A Walden
- A Whileman
- A Wilkinson
- A Williams
- A Williams
- A Wilson
- A Zak
- A Zaki
- Achille Iolascon
- Adam Auton
- Adam Brown
- Agnese Verzuri
- Agostino Ognibene
- Agostino Riva
- Ailsa Golightly
- Alan Maclean
- Alessandra
- Alessandra Stella
- Alessandra Vergori
- Alessia Giorli
- Alexander J Mentzer
- Alice Donati
- Alison M Meynert
- Alistair Nichol
- Ana da Silva Filipe
- Andrea Antinori
- Andrea Cossarizza
- Andrea Ganna
- Andrea Tommasi
- Andrew Rambaut
- Andrew Stenhouse
- Andy Law
- Anjali J Shastri
- Anna Canaccini
- Anna Maria Pinto
- Annarita Giliberti
- Annemarie B Docherty
- Antonella D'Arminio Monforte
- Antonia Ying Wai Ho
- Antonio Di Biagio
- Antony Symons
- Arianna Emiliozzi
- Arianna Gabrieli
- Audrey Coutts
- B Anwar
- B Attwood
- B Baines
- B Blackledge
- B Borislavova
- B Chandler
- B Charles
- B Creagh-Brown
- B David
- B Deacon
- B Deacon
- B Digby
- B Faulkner
- B Fuller
- B Gumbrill
- B Gurung
- B Hadebe
- B Hairsine
- B Hopkins
- B Johnston
- B Lenagh
- B Masunda
- B Ogg
- B Patel
- B Player
- B Purewal
- B Scholefield
- B Shelley
- B Sloan
- B Thomas
- B Wadams
- B Welsh
- B Wilkinson
- B Winter-Goodwin
- B Yates
- Baillie J Kenneth
- Barbara Rossetti
- Beale Rupert
- Beatrice Alex
- Benjamin Bach
- Bretherick Andrew D
- Bruno Frediani
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- C Dennis
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- C Stuart
- C Summers
- C Swan
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- C Wrey Brown
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- Carmen Marciano
- Caroline Abernathy
- Carrol Gamble
- Caterina Lo Rizzo
- Catherine A Shaw
- Catherine H Weldon
- Caulfield Mark
- Ceilia Boz
- Cesira Nencioni
- Chelsea Ye
- Chiara Fallerini
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- Chiara Spertilli
- Chloe Donohue
- Chris Ponting
- Christoper A Green
- Cinthia E Jannes
- Clare Jackson
- Clohisey Sara
- Cristina Mussini
- D Antcliffe
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- D Martin
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- D Tetla
- D Thornton
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- D Vedage
- D Walker
- D Warren
- D Williams
- D Wood
- D Wright
- Daniela Francisci
- Daniella Coker
- Danilo Tacconi
- David A van Heel
- David Bennet
- David L Robertson
- David Stuart
- Dawn Law
- Debby Bogaert
- Derek Murphy
- Domenico A Coviello
- E Abaleke
- E Allan
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- E Andrews
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- E B Jude
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- E Beranova
- E Bevan
- E Black
- E Brinkworth
- E Collins
- E Combes
- E Davies
- E Dobson
- E Dooks
- E Fisher
- E Gendall
- E Goff
- E Goodwin
- E Gordon
- E Heeney
- E Horsley
- E Hughes
- E Johnson
- E Knights
- E Lee
- E London
- E Maccacari
- E Massey
- E McKenna
- E Meadows
- E Moncur
- E Morino
- E Mwaura
- E Peasgood
- E Perkins
- E Radford
- E Raith
- E Raith
- E Salciute
- E Smith
- E Smithson
- E Stoddard
- E Stones
- E Thomas
- E Tilney
- E Timlick
- E Treus Gude
- E Virgilio
- E Watson
- E Wilby
- Edoardo Conticini
- Egle Saviciute
- Elena Bargagli
- Elena Desanctis
- Elisa Benetti
- Elisa Frullanti
- Elisabetta Menatti
- Elisabetta Schiaroli
- Ellie Mcmaster
- Emma C Thomson
- Emmanuelle Marques
- Enrico Martinelli
- Esther Duncan
- Esther Merlini
- Ewen M Harrison
- F Anderson
- F Auld
- F Bibi
- F Davies
- F Farquhar
- F Fisher
- F Hurford
- F Kibutu
- F McNeela
- F Moore
- F Nasir
- F Trim
- F Wakinshaw
- F Williams
- Fabio Lena
- Fawkes Angie
- Federico Anedda
- Federico Franchi
- Ferdinando Giannattasio
- Filip Taneski
- Filippo Aucella
- Filippo Biscarini
- Floriana Valentino
- Fourman Max Head
- Francesca Andretta
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- Furniss James
- G Andrew
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- G Bell
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- G Sera Howe
- G Sloane
- G Subramanian
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- G Turner
- G Watson
- G Wray
- Gabriella Coiro
- Gabriella Doddato
- Gail Carson
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- Gary Leeming
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- Giancarlo Bosio
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- Graham S Cooke
- Griffiths Fiona
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- H Reschreiter
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- H Sainsbury
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- H Tench
- H Tiveran
- H Turner
- H Whittle
- H Willis
- H Wood
- Haley Chris
- Hanning Mal
- Harrison David
- Hayley Hardwick
- Hayward Caroline
- Helen Szoor-McElhinney
- Hinds Charles
- Ho Antonia
- Horby Peter
- I Ali Mohamed Ali
- I Balagosa
- I Birkinshaw
- I Burn
- I Chadbourn
- I D Clement
- I Edmond
- I Frost
- I Hass
- I Hussain
- I Lancoma-Malcolm
- I Leadbitter
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- I Otahal
- I Turner-Bone
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- I White
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- Ilaria Meloni
- Immacolata Andolfo
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- J Allan
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- J Biddle
- J Birch
- J Birch
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- J Brown
- J Bryant
- J Butler
- J Camsooksai
- J Carter
- J Caterson
- J Cebrian Suarez
- J Cockerill-Taylor
- J Cole
- J Colley
- J Cooper
- J Cupitt
- J Cuttler
- J Daglish
- J Dasgin
- J Dawson
- J Dearden
- J Deery
- J Donnachie
- J Dykes
- J Easton
- J Egan
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- J Finn
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- J Gregory
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- J Jones
- J Jones
- J K Baillie
- J Kassam
- J Kenneth Baillie
- J Kenneth Baillie
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- McAuley Danny
- Meera Chand
- Meynert Alison
- Michelle Girvan
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- Wei Shen Lim
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- Wilson James F
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- Zheng Chenqing
- Publication venue
- Nature
- Publication date
- 01/01/2020
- Field of study
Get PDFHost-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 × 10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice
Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19
- Author
- ?ivko Iris
- Abbass Hakam
- Abdeladim Lilia
- Abdelhady Hesham
- Abdelkharim Hussam
- Abdelrazik Marwa
- Abdi Zakee
- Abdukahil Sheryl Ann
- Abel Lynn
- Abraham Jacinta
- Abrahamson Gail
- Abusamra Yousuf
- Aceto Romina
- Adams Nick
- Adams Peter
- Adebambo Olumide
- Adhikari Neill
- Adhikari Sheetal
- Affleck Julia
- Agha Gloria
- Aghemo Alessio
- Agno Ronan
- Ahmad Norfaizan
- Ain Quratul
- Ainscough Kate
- Ainsworth James
- Aitken Lindianne
- Akamp Ceren
- Al Enezi Farhan
- Al-Bassam Wisam
- Al-Beidh Farah
- Albert Martin
- Albrett Jonathan
- Alderman Meera
- Aldo Bonizzoni Matteo
- Alegria Ana
- Alessandro Carà Gianmarco
- Alexander Brian
- Alexander Peter
- Alfonso Jordan
- Ali Maryam
- Ali Murtaza
- Allam Hayat
- Allen Barbara
- Allen Louise
- Allibone Suzanne
- Almeshhedani Hasham
- AlQahtani Samah
- Alswaidan Lolowa
- Altomy Mohammed
- Al Amri Ali
- Al Qasim Eman
- Amatya Sameena
- Ambrosino Richard
- Anderson Thomas
- Andreae Mark
- Aneman Anders
- Angus Derek C.
- Anjum Aisha
- Ankert Juliane
- Annane Djillali
- Anne-Laure Fedou
- Anstey Matthew
- Antcliffe David
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- Antoine Pierre
- Antoine Studer
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- Arabi Yaseen M.
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- Garrier Ludivine
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- Garton Mark
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- Gascoyne Rachel
- Gattas David
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- Ghaffari Mehrdad
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- Ghosh Alison
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- Gibbins Alexandra
- Gill Mandy
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- Gladas Kirsty
- Glasby Kathleen
- Gledhill Lisa
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- Glynou Loukia
- Goddard Wendy
- Godement Mathieu
- Godoy Lucas C.
- Goebeler M.E.
- Golden David
- Goldman John
- Goligher Ewan
- Gomez Keith
- Gommans Frank
- Goodwin Jayne
- Goossens Herman
- Gopal Shameer
- Gopinath Amitha
- Goralski Patricia
- Gordon Anthony C.
- Gosbell Iain
- Gould Richard
- Grady Bart
- Graham Cheryl
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- Graniewski Jaroslaw
- Grant Caroline
- GrauNovellas Neus
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- Guérin Emmanuelle
- Gómez Francisco
- Göpel Siri
- Habeichi Wadih
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- Hagel Stefan
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- Haidar Ghady
- Haider Nafeesah
- Haider Syeda
- Hajdu Bence
- Hakak Sheeba
- Halden Sandra
- Haldeos Anne
- Hall Alistair S
- Hall Amelia
- Hall Andrew
- Hall Kathryn
- Hall Rebecca
- Hamilton David
- Hamilton-Davies Colin
- Hamlyn Vincent
- Hammond Naomi
- Hammonds Fiona
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- Harris Jade
- Harris John
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- Harrison Susan
- Harrow Kath
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- Harvala-Simmonds Heli
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- Headlam Evie
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- Hensley Joseph
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- Hernandez Erik
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- Hey Samuel
- Hickey John
- Hierons Sarah
- Higgins Alisa M.
- Hill Claire
- Hill Dianne
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- Hilldrith Anette
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- Hodge Christopher
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- Hornsby James
- Horton Michelle
- Horvat Christopher M.
- Howcroft Clare
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- Hower Martin
- Howie Lucy
- Howle Ryan
- Hoxha Elvira
- Huang David T.
- Hughes Debbie
- Hugill Keith
- Huijbens Danique
- Hullegie Sebastiaan
- Hulley Amanda
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- Jan Hassing Robert
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- Jarczak Dominik
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- Jongebloed Katherine
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- Karachi Tim
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- Karlikowski Michal
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- Kasipandian Vidya
- Kassir Sandy
- Katary Amro
- Kato Hideaki
- Kavanagh Lisa
- Kayani Abdul
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- Kaye Callum
- Kazi Aayesha
- KC Shirish
- KC Shirsh
- Keating Liza
- Keatley Claire
- Keeler Sheryl
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- Keijzer-Timmers Nicole
- Kell Kay
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- Kelsall Olivia
- Kendrick Sara
- Kernan Maeve
- Kerslake Ian
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- Khade Reena
- Khalid Imrana
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- Khanal Sushil
- Khare Divya
- Khoso Nasir
- Khoud Ahmed
- Khwaja Kosar
- Kidwai Aneela
- Kiiski Heikki
- Kilner Mari
- Kim Edy Y.
- Kimpton Sarah
- King Andrew
- Kinney Fiona
- Kirk Jill
- Kirk Rosemary
- Kirkby Amy
- Kirkham Simon
- Kit Barbara
- Kitsios Georgios
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- Klein Daniela
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- Kluge Stefan
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- Kochanek Matthias
- Kochert Erik
- Koelink Maaike
- Koirala Kanchan
- Koirala Sabin
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- Kolovou Angeliki
- Konecny Pam
- Kong Jing
- Koopmans Matty
- Kosa Alma
- Kremling Julius
- Kreß Gabriele
- Krishnamoorthy S
- Krishnamurthy Vinodh
- Kruger Peter
- Kruisdijk-Gerritsen Arriette
- Kruisselbrink Rebecca
- Kuitunen Anne
- Kumar Anand
- Kumar Nikhil
- Kumar Rohit
- Kummerlen Christine
- Kunishima Hiroyuki
- Kunwar Puja
- Kunz Kevin
- Kurenda Catherine
- Kutsogiannis Demetrios
- Kuybida Yuriy
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- Kyeremeh Lynsey
- Kyle Laura
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- Labbe Vincent
- Laffan Mike
- Laffey John
- Laha Shondipon
- Lai Vivian
- Lambert Bridget
- Lamontagne Francois
- Lampro Lamprini
- Landais Michaël
- Landoni Giovanni
- Landsiedel-Mechenbier Elke
- Lang Eva
- Langridge Emma
- Latham Victoria
- Latino Reece
- Laudi Svenja
- Laugs Fabian
- Lavana Jayshree
- Laver Russell D.
- Law Daniel
- Lawler Patrick R.
- Le Basnier Elliot
- Le Guen Lenaïg
- Le Loup Guillaume
- Leaf David E.
- Lean Richard
- Leaver Susannah
- Leavis Helen
- Leblond Julie
- Leditschke Anne
- Lee Kelvin
- Lee Stephanie
- Lee Stephen
- Lefevre Montaine
- Leffelaar Evelien
- Lehalleur Adrien
- Lellouche Francois
- Lemaire-Brunel Delphine
- Lembo Rosalba
- Leparco Cécile
- Leroyer Marie-Helene
- Lesona Eden
- Levett Chris
- Lewis Joanne
- Lewis Roger J.
- Lewis Sarah
- LewisProsser Lorraine
- Liao Angela
- Lim Rosario
- Limb James
- Lindergard Gabriella
- Linnett Vanessa
- Linstrum Kelsey M.
- Litton Ed
- Litton Edward
- Liu Theresa
- Lizotte Patricia
- Lock Stephen
- Lockett Teresa
- Logan Meg
- Lomme Kaatje
- Long Matilda
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- Lother Sylvain
- Lowe Benjamin
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- Luis David
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- Luo Ji
- Lye Alison
- Lynch Ceri
- Lynch Daniella
- López Maria
- López Rafael
- Löbel Madlen
- MacKay Callum
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- MacKay Lynn
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- MacLennan Sheila
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- Madani Yasser
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- Maharajh Amitaa
- Maharjan Mili
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- Maharjan Sabi
- Maiden Matthew
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- Major Emmet
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- Marchesi Mattia
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- Marin-Corral Judith
- Marin?ek Martin
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- Marion Beuzelin
- Markota Andrej
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- Marriott Yvonne
- Marroquin Oscar
- Marsden Tracy
- Marsh Emma
- Marshall John C.
- Marshall Lucy
- Marten Nicole
- Martin Elise
- Martin Emma
- Martin Jane
- Martin Laila
- Martin Timothy
- Martin-Lazarro Juan
- Martinez Maria
- Martucci Antonio
- Martynoga Robert
- Mary-Genetu Roman
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- Maselli Astrid
- Mason Alexina
- Mason Brittany
- Masood Sobia
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- Masse Marie-Helene
- Massey Natalie
- Masters Kristy
- Mataliotakis Michail
- Mathew Meghena
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- Matimba-Mupaya Wadzanai
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- Matthews Julie
- Maxime Virginie
- Mayak Katelyn
- Mayangao Irving
- Maynard Victoria
- Mayr Florian
- Mc-Kenzie Josette
- McAdams David
- McArthur Colin J.
- McAuley Daniel F.
- McAuley Julie
- McCallion Edmund
- McCarthy Aine
- McClintock Declan
- McConnochie Rachael
- McCracken Phoebe
- McCreary Erin
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- McCullagh Iain
- McCullagh Liz
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- McCullough James
- McDonald Bree
- McDyer John
- McEldrew Ben
- McEldrew Rebecca
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- McGain Forbes
- McGarry Karen
- McGhee Christopher
- McGlothlin Anna
- McGloughlin Steve
- McGlynn Deborah
- McGoldrick Clare
- McGuigan Peter
- McGuinness Shay P.
- McIntyre Joanne
- McIntyre Lauralyn
- McKee Madeleine
- McKenna Shirley
- McKenna Sonia
- Mckeon Laurie
- Mclaughlan Danielle
- McMaster Moyra
- McMillan Alexandra
- McMillan Catherine
- McMillan Helen
- McMorrow Liam
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- McNamara Robert
- McNicholas Bairbre
- McQuilten Zoe
- McVerry Bryan J.
- McWilliam Stephen
- Medhurst Laura
- Medva Rebecca
- Meermeier Werner
- Megarbane Bruno
- Mehrtens Jan
- Mehta Reena
- Meijer Karina
- Menon David
- Mercier Emmanuelle
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- Mevavala Bhaumik
- Mew Louise
- Meyer Jason
- Mezher Chaouki
- Meziani Ferhat
- Mfuko Celina
- Mguni Nhlanhla
- Michael Angiy
- Michalak-Glinska Natalia
- Middledorp Saskia
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- Mikusek Justyna
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- Millen Tina
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- Miln Rebecca
- Minnier Tami
- Mistry Deena
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- Mitchard Sarah
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- Moghbeli Kaveh
- Mohammed Amal
- Moine Pierre
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- Monaghan Holly
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- Moneger Guy
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- Morel Guillaume
- Morgan Karen
- Morgan Matt
- Morgan Stacey
- Morpeth Susan
- Morris Anna
- Morris Jenny
- Morris Lucy
- Morris Sheila
- Morrison Lynette
- Mouncey Paul R.
- Mowery Brent
- Mrad Aymen
- Mtuwa Shelia
- Mukherjee Dipak
- Mulder John
- Mulier Jelle
- Mulla Suleman
- Mullan Dee
- Muller Grégoire
- Munt Sheila
- Murphy Aisling
- Murphy Lorna
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- Murphy Ryan
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- Murray Andrew
- Murray Lauren
- Murray Lyle
- Murthy Srinivas
- Music Edvin
- Muteithia Margaret
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- Muñoz-Bermúdez Rosana
- Mwaura Esther
- Mwembani Tina
- Naeem Anas
- Naidu Brintha
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- Nair Priya
- Nakamuro Hiromi
- Nakazono Kenichi
- Nakhnoukh Cristina
- Nand Kiran
- Nandani Aarti
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- Naz Mobeena
- Neal Matthew
- Nee Jens
- Neill Andy
- Nelli Apoorva
- Nemeth Christopher
- Nemeth-Roszpopa Karolina
- Netea Mihai
- Netherton Kimberley
- Neto Ary
- Newbould David
- Newlands Jessica
- Newman Julie
- Newman Tabitha
- Ng Anthony
- NG Christopher
- Nguyen Philippe
- Nguyen-Valat Thi-My-Hue
- Nichol Alistair D.
- Nicholier Tiphaine
- Nicholson Andrew
- Nicholson Anne
- Nicholson Sarah
- Nickoleit-Bitzenberger Daniela
- Nierhaus Axel
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- Nolan Jerry
- Nordin Nazril
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- Nourse Mary
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- Nygren Maria
- O Rourke Kate
- O'Connell Martin
- O'Kell Eleanor
- O'Neill Lorraine
- O'Neill Stephen
- O'Reilly Joanna
- O?Brien Julie
- O?Brien Neale
- O?Connor Aibhilin
- O?Connor Anne
- O?Connor Caroline
- O?Connor Stephanie
- O?Dwyer Michael
- O?Halloran Sinead
- O?Kane Cecilia
- O?Kane Sinéad
- O?Leary Ryan
- O?Malley Laura
- O?Neill Aisling
- O?Reilly Kevin
- Oakley Susan
- Oborska Aneta
- Occhipinti Giovanna
- Ochin Evelina
- Oczkowski Simon
- Ogg Bethan
- Ogungbenro Kayode
- Okubanjo Maryanne
- Okundaye Clementina
- Oliver Anne
- Oliver Martyn
- Omer Nimca
- Oncea Lynne
- Orford Neil
- Oritz-Ruiz de Gordoa Laura
- Orlikowska Izabela
- Orlikowski David
- Orr Katrina
- Osagie Rawlings
- Osborne Alexander
- Osborne Jason
- Osinga Margreet
- Ostermann Marlies
- Ottens Thomas
- Owen David R. J.
- Oza Deepali
- Padmakumar Anand
- Page Shannon
- Page Valerie
- Pakats Mari-Liis
- Pakou Glykeria
- Palermo Annamaria
- Paneru Hem
- Panjwani Ashok
- Panwar Rakshit
- Pappa Evita
- Paramasivam Elankumaran
- Parekh Dhruv
- Parikh Harshel G.
- Parke Rachael L.
- Parker Jane C.
- Parker Lorraine
- Parker Natasha
- Parmar Dinesh
- Parry-Billings Karen
- Parsons Penny
- Pasieka Bastian
- Patanwala Asad
- Patawala Asad
- Patch Sarah
- Patel Amit
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- Patel Kamal
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- Pathak Shreya
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- Patterson Lisa
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- Peake Sandra
- Pearson Harriet
- Pearson Karen
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- Pegler Suzannah
- Pellicano Susan
- Pemberton Abigail
- Pendlebury Jessica
- Pereira Rita
- Pereira Tiago Nuno Alfaro Lima
- Perez Jane
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- Peters Sam
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- Petros Sirak
- Pettilä Leena
- Pettilä Ville
- Phalod Gunjan
- Philbin Jennifer
- Philip Annlin
- Philippe Rigaud
- Phillips Barbara
- Phillips Matt
- Phua Jason
- Phull Mandeep-Kaur
- Phuyal Aarti
- Pickering Charlotte
- Pickkers Peter
- Piercy Charlie
- Pietersma Mario
- Pillai Suresh
- Pinder Meredith
- Pinnell Jez
- Pinto Marta
- Pitts Sally
- Piva Simone
- Plantefeve Gaetan
- Platenkamp Ellen
- Plesnikova Yvonna
- Pletz Mathias
- Plummer Bethany
- Plummer Mark
- Pogreban Tatiana
- Pogson David
- Polfliet Margot
- Polgarova Petra
- Polley Grace
- Pollock Katrina M.
- Pomeroy Fiona
- Poojara Latesh
- Pooni Jagtar- Singh
- Porteous Rebecca
- Porter David
- Postlethwaite Kelly
- Postma Douwe
- Potter Alison
- Potter Sarah
- Poulter Amber-Louise
- Poupblanc Séverine
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- Pourcine Franck
- Povoa Pedro
- Powell Elizabeth
- Prabakaran Rajalakshmi
- Pradel Gael
- Pratheema Ramachandran
- Prebeg Katharina
- Preijers Lieke
- Presneill Jeffrey
- Pridee Nicole
- Prinssen Anton
- Pritchard Kelly
- Proudfoot Nicola
- Prout Rachel
- Pugh Richard
- Purandare Laura
- Purnell Rebecca
- Purohit Dharam
- Purvis Sarah
- Puskarich Michael
- Putensen Daniel
- Puthucheary Zudin
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- Pérez-Terán Purificación
- Põldots Liisi
- Qiu Shan
- Qiu Xinyi
- Quayle Rachael
- Quenot Jean Pierre
- Quinn Alison
- Quinn Kevin
- Qureshi Hafiz
- Raczek James
- Rad Laura
- Rademaker Emma
- Rahmani Hassene
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- Raithatha Ajay
- Raj Ashok
- Ralston Maximillian
- Ramakrishnan N
- Ramali Mohamed
- Ramamurthi Balaji
- Ramanan Mahesh
- Ramos Angelo
- Ramos Lidia
- Randell Georgina
- Rangan Ritika
- Ranganathan Lakshmi
- Rao Deepak
- Rashan Aasiyah
- Rashan Sumayyah
- Ratcliffe Megan
- Ratnam Valli
- Ravry Celine
- Rawlins Sam
- Reay Michael
- Rebello Rashmi
- Reddy Amie
- Reddy Harsha
- Reed Catherine
- Rees Stephanie
- Reeve Brenda
- Regli Adrian
- Rehman Atique
- Reid Andrew
- Reid Liadain
- Reidy Bryan
- Reill Lorenz
- Reinhard Veronika
- Rengers Els
- Rennit Pille
- Reschreiter Henrik
- Reverté-Villarroya Silvia
- Revill Adam
- Rewa Oleksa
- Reyes Luis Felipe
- Reynolds Bob
- Reynolds Claire
- Reynolds Jessica
- Rhodes Jonathan
- Richards Carol
- Richards Suzanne
- Richards-Belle Alvin
- Richardson Aaron
- Richardson Angus
- Richecoeu Jack
- Riches Joanne
- Ricketts Dan
- Ricketts Daniel
- Riddell Phillip
- Riepe Ansgar
- Rietveld Ilse
- Rimmer Dominic
- Ripa Marco
- Rissen Reimer
- Ristimäki Sanna
- Ritzema Jenny
- Rivett Justine
- Rizzoni Damiano
- Roberts Belinda
- Roberts David
- Roberts Eilir
- Roberts Tracey
- Robertson Debra
- Robinson Matt
- Roche Lisa
- Roche-Campo Ferran
- Rochwerg Bram
- Rodden Natalie
- Rodriguez Marina
- Rodríguez-Gómez Jorge
- Roebers Harald
- Roedl Kevin
- Rohde Gernot
- Rojo Roceld
- Romagnuolo Tina
- Roman Jaime
- Romberg Birgit
- Rook Clare
- Rooney Kevin
- Roovers Noortje
- Rosaroso Lace
- Rosborough Brian
- Rose Steve
- Rosenstein-Sisson Rachel
- Ross Elizabeth
- Rostron Anthony
- Roth Jason
- Rouge Patrick
- Roumen Rudy
- Rounds Charles
- Rovere-Querini Patrizia
- Rowan Kathryn M.
- Rowe-Leete Louise
- Rowland Matthew
- Roy Alistair
- Roynon-Reed Anna
- Rueß-Paterno Giusi
- Ruiz Winningtom
- Runge Isabelle
- Ruselli Giovanna
- Russo Giada
- Ryalls Kim
- Ryan Donal
- Ryan Lucy
- Sabaretnam Suganya
- Sabelhaus Timo
- Sackrowitz Rachel
- Sadera Girendra
- Sadique Zia
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- Saha Sian
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- Saito Hiroki
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- Salahuddin Nawal
- Salberg Armorel
- Saleem Malik
- Salhi Sara
- Sall Jas
- Salmon Charlotte
- Salmon Karen
- Saluja Rupali
- Saluzzio Romina
- Salvati Stefano
- Sampson Julia
- Sanders Arnate
- Sanderson Amanda
- Sandhu Gyan
- Sanghavi Ritesh
- Santamaria John
- Santos Filipa
- Santos Marlene S.
- Sapsford David
- Sara Treena
- Saran Anita
- Sathe Sonia
- Sathianathan Kushaharan
- Sathianathan Prasannakumari
- Saull Michelle
- Saunders Christina T.
- Saunderson Paula
- Sauras-Colón Esther
- Saxena Manoj
- Sayada Sarah
- Sayehli Cyrus
- Scanlan Jeremy
- Scano Riccardo
- Schaaf Bernhard
- Schlegel Christian
- Schmidhofer Mark
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- Schoenling Andrew
- Scholl Denise
- Schotsman Joost
- Schouten Jeroen
- Schueler Robert
- Schuster-Bruce Martin
- Schutgens Roger
- Schweikert Sacha
- Scott Kathryn
- Scott Zoe
- Scully Michael
- Seaman Rebecca
- Seidel Antje
- Seidu Fatima
- Seigne Patick
- Sekiwala Rose
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- Selmi Carlo
- Sement Arnaud
- Senya Ho
- Seppelt Ian
- Sernicola Elisa
- Serri Karim
- Sevilla Chanthou
- Seymour Christopher W.
- Shah Faraaz
- Shahid Tasnin
- Shaikh Arif
- Shaikh Mohiuddin
- Shakya Roshni
- Shankar-Hari Manu
- Sharma Deepak
- Shaw David
- Shaw Deborah
- Shaw Joanne
- Shearer Audrey
- Sheath Ben
- Sheffield Jonathan
- Shehabi Yahya
- Shekar Kiran
- Shelton Sarah
- Sherwood Nick
- Shetty Varun
- Shields Fiona
- Shimabukuro-Vornhagen Alexander
- Shintani Ayumi
- Shirley Kim
- Shovelton Charmaine
- Shree Madhu
- Shrestha Namrata
- Shrestha Sabita
- Shrestha Tapaswi
- Shu Ki Lok Jennifer
- Shyamsundar Murali
- Siami Shidasp
- Sibin Sindhu
- Sicat Christine
- Siddiqui Atif
- Siddiqui Ayesha
- Sidéris Georgios
- Siewerski Chris
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- Wyatt Rachel
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- Yamagishi Yoshiaki
- Yamashita Chizuru
- Yang Yang
- Yarad Elizabeth
- Yates Bryan
- Yates David
- Yealy Donald
- Young Ian
- Young Meredith
- Young Paul
- Youngstein Taryn
- Yu Haili
- Yusuff Hakeem
- Zaharia Mihaela
- Zaidi Abbas
- Zaki Ahmed
- Zaman Mohsin
- Zarychanski Ryan
- Zdanavidiene Ausra
- Zhao Xiao
- Zinzoni Vanessa
- Zitter Letizia
- Zouita Louisa
- Publication venue
- 'American Medical Association (AMA)'
- Publication date
- 11/04/2023
- Field of study
Get PDFIMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.
Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.
DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).
INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days.
MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.
RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).
CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570
Mapping the human genetic architecture of COVID-19
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- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2021
- Field of study
Get PDFThe genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease
Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity
- Author
- Abaleke E.
- Abdelrazik M.
- Abedalthagafi M.
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- Al-Sarraj Y.
- Alaamery M.
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- Woodyatt W.
- Worner R.
- Wraith E.
- Wray G.
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- Wulandari R.
- Wynter I.
- Xavier K.
- Yang J.
- Yang Z.
- Yates B.
- Young M.
- Yussuf S.
- Zak A.
- Zaki A.
- Zamikula J.
- Zanella I.
- Zarebska-Michaluk D.
- Zeberg H.
- Zechner M.
- Zguro K.
- Zhai R.
- Zheng C.
- Zitter L.
- Zongo O.
- Zucchi P.
- Zuccon U.
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2022
- Field of study
No full textThe combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management
Long-term (180-Day) outcomes in critically Ill patients with COVID-19 in the REMAP-CAP randomized clinical trial
- Author
- Abbass H
- Abdeladim L
- Abdelhady H
- Abdelkharim H
- Abdelrazik M
- Abdi Z
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- Publication venue
- 'American Medical Association (AMA)'
- Publication date
- 30/11/2022
- Field of study
No full textImportance The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown. Objective To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes. Design, Setting, and Participants Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022. Interventions Patients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401). Main Outcomes and Measures The main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83. Results Among 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06 [95% CrI, 0.82-1.38]) and the probabilities of harm from hydroxychloroquine (96.9%; HR, 1.51 [95% CrI, 0.98-2.29]) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%; HR, 1.61 [95% CrI, 0.97-2.67]) were high. The corticosteroid domain was stopped early prior to reaching a predefined statistical trigger; there was a 57.1% to 61.6% probability of improving 6-month survival across varying hydrocortisone dosing strategies. Conclusions and Relevance Among critically ill patients with COVID-19 randomized to receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality compared with patients randomized to the control, and treatment with an antiplatelet had a 95.0% probability of improved 180-day mortality compared with patients randomized to the control. Overall, when considered with previously reported short-term results, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months
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GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19
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- Abedalthagafi M
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- Cabral-Ortega L
- Cabrelli L
- Caceres-Agra JJ
- Cagova L
- Calbo E
- Calderón EJ
- Cale E
- Callaghan M
- Callam S
- Calvo CM
- Camacho S
- Campbell A
- Campbell B
- Campbell H
- Campbell R
- Campbell S
- Campos MC
- Campos S
- Camsooksai J
- Candalija AC
- Candon AM
- Capitán CF
- Capozzi L
- Capps N
- Carbonell C
- Cardona-Huerta S
- Cardwell A
- Carioca AAF
- Carmody M
- Carmody S
- Carnahan M
- Carpintero MS
- Carracedo A
- Carracedo A
- Carratto TMT
- Carrera LG
- Carrillo-Avila JA
- Carson G
- Cart C
- Carter A
- Carter D
- Carter E
- Carter J
- Carter M
- Carter S
- Cartlidge D
- Carungcong J
- Carvalho MCC
- Casasnovas C
- Casey M
- Castano L
- Castaño CF
- Castaño JAT
- Castelao JE
- Castillo MA
- Caswell M
- Caterson J
- Cathcart S
- Catlow L
- Cavazza A
- Cave A
- Cawley K
- Cawley K
- Cawthron K
- Cañadas Y
- Ceballos FC
- Cha M
- Chablani M
- Chadwick R
- Chan R
- Chand M
- Chandler B
- Chandna H
- Chapman S
- Charles B
- Charlesworth R
- Charnock R
- Charris HM
- Chaux JG
- Chaves-Santiago WG
- Chechi K
- Cheema Y
- Chen J
- Cherian S
- Chesters K
- Chetam L
- Cheyne C
- Chikowore P
- Childs D
- Chiquillo-Gómez S
- Chisholm C
- Choudhr O
- Choudhury Y
- Chukkambotla S
- Chávez MEQ
- Cid-Lopez MA
- Cienfuegos-Jimenez O
- Cinquina Z
- Clamp S
- Clapham M
- Clarey E
- Claridge H
- Clark A
- Clark A
- Clark M
- Clark M
- Clark R
- Clark R
- Clark S
- Clark S
- Clark V
- Clarke N
- Clarkson M
- Clayton S
- Clement I
- Clements S
- Clohisey S
- Coates C
- Cochrane P
- Cockerill H
- Cockrell M
- Coe R
- Coetzee S
- Coghlan P
- Cohrane C
- Coker D
- Cole J
- Cole J
- Cole S
- Coleman C
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- Coles H
- Colley J
- Colley N
- Collier D
- Collier D
- Collier H
- Collins A
- Collins C
- Collins E
- Collins E
- Collins K
- Collins K
- Collins R
- Collins V
- Collis M
- Combes E
- Conde-Vicente R
- Conejo IP
- Connell J
- Connolly K
- Connor M
- Convery K
- Conyngham J-A
- Cooke GS
- Cookson R
- Cooper J
- Cooper L
- Cooper L
- Corcoran E
- Corcoran K
- Cordero-Lorenzana ML
- Corella D
- Corin C
- Cornell S
- Cornell T
- Corner A
- Corral MA
- Corrales A
- Cortes-Sanchez JL
- Corton M
- Cosgrove D
- Cosier T
- Costa TX
- Cother N
- Coton Z
- Cottam L-J
- Cottle J
- Coulding M
- Coutts A
- Coventry T
- Covernton P
- Cowley A
- Cowley N
- Cowton A
- Cox A
- Coyle J
- Craig H
- Craig J
- Crawley R
- Creagh-Brown B
- Crew A
- Crickmore V
- Cristiano D
- Croft M
- Crowe R
- Crowley M
- Cruz C
- Cruz MS
- Cruz R
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- Csabi P
- Cuerda VM
- Cuesta L
- Cullum L
- Cunha GCR
- Cunningham A
- Cunningham M
- Cupitt J
- Curgenven H
- Currie S
- Cusack R
- Cutler S
- Cutting P
- Cutts S
- Da Gloria EF
- Da Rocha J
- da Silva Filipe A
- da Silva GV
- Daglish J
- Dagutao Z
- Dale K
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- Dalmau D
- Dalton C
- Dalton J
- Daly Z
- Dalziel J
- DAmato F
- Dance A
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- Daniel E
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- Dark P
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- Dawson A
- Dawson D
- Day A
- Day N
- de Andrés R
- de Araújo JNG
- De Beger S
- de Bustamante AD
- de Gordoa LO-R
- de Heredia ML
- de Juan C
- De la Cruz Troca J
- de la Horra C
- de la Hoz AB
- De Martino-Rodríguez A
- de Neef M
- De Queiroz JG
- de Quirós FGB
- de Silva T
- de Sousa Alves Neri JL
- Deacon B
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- Debreceni G
- Deery J
- del Campo-Pérez V
- Dela Rosa A
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- Dexter C
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- Dickson H
- Dietl B
- Digby B
- Digby S
- Ding L
- Diz-de Almeida S
- Djeugam B
- Doble P
- Dobson E
- Docherty AB
- Dodd A
- Dodds S
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- Domingos P
- Domínguez-Garrido E
- Donaldson A
- Donaldson D
- Donegan C
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- Donohue C
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- Doonan R
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- dos Santos KA
- Douglas K
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- Durrant G
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- D’Sylva S
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- Earl V
- Eastgate C
- Easthope A
- Easthope A
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- English K
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- España PP
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- Fernandez-Nestosa MJ
- Fernandez-Roman J
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- Fernández FA
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- Fernández-Robelo U
- Fernández-Rodríguez A
- Fernández-Sampedro M
- Fernández-Sánchez R
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- Ferrero SF
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- Fuentes CS
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- Gagliardi L
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- Gallo JPV
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- García FR
- García I
- García L
- García M
- García MG
- García PM
- García-de-Vicuña A
- García-García I
- García-Ibarbia C
- García-Montero AC
- García-Soidán A
- García-Vázquez E
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- Gude ET
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- Gulati A
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- Íñiguez M
- Publication venue
- Springer Nature
- Publication date
- 17/05/2023
- Field of study
Get PDFData availability: Downloadable summary data are available through the GenOMICC data site (https://genomicc.org/data). Summary statistics are available, but without the 23andMe summary statistics, except for the 10,000 most significant hits, for which full summary statistics are available. The full GWAS summary statistics for the 23andMe discovery dataset will be made available through 23andMe to qualified researchers under an agreement with 23andMe that protects the privacy of the 23andMe participants. For further information and to apply for access to the data, see the 23andMe website (https://research.23andMe.com/dataset-access/). All individual-level genotype and whole-genome sequencing data (for both academic and commercial uses) can be accessed through the UKRI/HDR UK Outbreak Data Analysis Platform (https://odap.ac.uk). A restricted dataset for a subset of GenOMICC participants is also available through the Genomics England data service. Monocyte RNA-seq data are available under the title ‘Monocyte gene expression data’ within the Oxford University Research Archives (https://doi.org/10.5287/ora-ko7q2nq66). Sequencing data will be made freely available to organizations and researchers to conduct research in accordance with the UK Policy Framework for Health and Social Care Research through a data access agreement. Sequencing data have been deposited at the European Genome–Phenome Archive (EGA), which is hosted by the EBI and the CRG, under accession number EGAS00001007111.Extended data figures and tables are available online at https://www.nature.com/articles/s41586-023-06034-3#Sec21 .Supplementary information is available online at https://www.nature.com/articles/s41586-023-06034-3#Sec22 .Code availability:
Code to calculate the imputation of P values on the basis of SNPs in linkage disequilibrium is available at GitHub (https://github.com/baillielab/GenOMICC_GWAS).Acknowledgements: We thank the members of the Banco Nacional de ADN and the GRA@CE cohort group; and the research participants and employees of 23andMe for making this work possible. A full list of contributors who have provided data that were collated in the HGI project, including previous iterations, is available online (https://www.covid19hg.org/acknowledgements).Change history: 11 July 2023: A Correction to this paper has been published at: https://doi.org/10.1038/s41586-023-06383-z. -- In the version of this article initially published, the name of Ana Margarita Baldión-Elorza, of the SCOURGE Consortium, appeared incorrectly (as Ana María Baldion) and has now been amended in the HTML and PDF versions of the article.Copyright © The Author(s) 2023, Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).GenOMICC was funded by Sepsis Research (the Fiona Elizabeth Agnew Trust), the Intensive Care Society, a Wellcome Trust Senior Research Fellowship (to J.K.B., 223164/Z/21/Z), the Department of Health and Social Care (DHSC), Illumina, LifeArc, the Medical Research Council, UKRI, a BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070 and BBS/E/D/30002275) and UKRI grants MC_PC_20004, MC_PC_19025, MC_PC_1905 and MRNO2995X/1. A.D.B. acknowledges funding from the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z), the Edinburgh Clinical Academic Track (ECAT) programme. This research is supported in part by the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant MC_PC_20029). Laboratory work was funded by a Wellcome Intermediate Clinical Fellowship to B.F. (201488/Z/16/Z). We acknowledge the staff at NHS Digital, Public Health England and the Intensive Care National Audit and Research Centre who provided clinical data on the participants; and the National Institute for Healthcare Research Clinical Research Network (NIHR CRN) and the Chief Scientist’s Office (Scotland), who facilitate recruitment into research studies in NHS hospitals, and to the global ISARIC and InFACT consortia. GenOMICC genotype controls were obtained using UK Biobank Resource under project 788 funded by Roslin Institute Strategic Programme Grants from the BBSRC (BBS/E/D/10002070 and BBS/E/D/30002275) and Health Data Research UK (HDR-9004 and HDR-9003). UK Biobank data were used in the GSMR analyses presented here under project 66982. The UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government, British Heart Foundation and Diabetes UK. The work of L.K. was supported by an RCUK Innovation Fellowship from the National Productivity Investment Fund (MR/R026408/1). J.Y. is supported by the Westlake Education Foundation. SCOURGE is funded by the Instituto de Salud Carlos III (COV20_00622 to A.C., PI20/00876 to C.F.), European Union (ERDF) ‘A way of making Europe’, Fundación Amancio Ortega, Banco de Santander (to A.C.), Cabildo Insular de Tenerife (CGIEU0000219140 ‘Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19’ to C.F.) and Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC20/57 to C.F.). We also acknowledge the contribution of the Centro National de Genotipado (CEGEN) and Centro de Supercomputación de Galicia (CESGA) for funding this project by providing supercomputing infrastructures. A.D.L. is a recipient of fellowships from the National Council for Scientific and Technological Development (CNPq)-Brazil (309173/2019-1 and 201527/2020-0)
Mapping the human genetic architecture of COVID-19
- Author
- Abdelrazik M
- Abdullah T
- Abe R
- Abe S
- Abecasis GR
- Abel L
- Abernathy C
- Abraheem A
- Abul-Husn NS
- Acosta-Herrera M
- Acquilini D
- Acquilini D
- Adachi T
- Adachi Y
- Adams C
- Adams K
- Adanini O
- Adeleye O
- Adeniji K
- Adra D
- Afifi N
- Afilalo J
- Afilalo M
- Afolabi D
- Afrasiabi Z
- Afset JE
- Agasou A
- Aghemo A
- Agranoff D
- Agrawal S
- Aguirre LA
- Agwuh K
- Ahmad HF
- Ahmad N
- Ahmed A
- Ahmed C
- Ahmed KA
- Ai M
- Ail D
- Akeroyd L
- Akhtar MN
- Akhtar S
- Akinkugbe O
- Aksentijevich A
- Al Thani A
- Al-Muftah W
- Al-Sarraj Y
- Alarcon C
- Alarcon-Riquelme ME
- Alasdair F
- Alaverdian D
- Alavere H
- Albertos R
- Albillos A
- Albrecht W
- Albrich W
- Albrich WC
- Aldera EL
- Aldridge J
- Alegria A
- Alex B
- Alexander P
- Alfonso J
- Algera AG
- Ali A
- Ali IMA
- Ali S
- Aliberti S
- Allan A
- Allan E
- Allan J
- Alldis Z
- Allen L
- Allen S
- Allibone S
- Allison KS
- Allos R
- Ally SM
- Almaden-Boyle C
- Altabaibeh A
- Altmueller J
- Alvaro A
- Amar D
- Amin V
- Amitrano S
- Amiya S
- Ampuero J
- Anan R
- Anania S
- Anastasescu E
- Anderson F
- Anderson J
- Anderson M
- Anderson P
- Anderson S
- Anderson S
- Anderson T
- Ando A
- Andolfo I
- Andrade V
- Andretta F
- Andreucci E
- Andreucci E
- Andrew A
- Andrew B
- Andrew G
- Andrews E
- Andrews SJ
- Andrews SJ
- Andrews SJ
- Andrews SJ
- Andrikopoulos P
- Anedda F
- Aneli S
- Anemoli V
- Angelini C
- Angus B
- Annis A
- Antcliffe D
- Antinori A
- Antoni MD
- Anumakonda V
- Anwar M
- Anzai T
- Apetri E
- Arai D
- Arana E
- Arbane G
- Archer K
- Arciero E
- Arden T
- Arias SS
- Arif S
- Arimura K
- Armstrong J
- Armstrong JA
- Armstrong L
- Armstrong R
- Arning N
- Arnold S
- Arora J
- Artuso R
- Arumugam P
- Asakura T
- Asano K
- Aschard H
- Ascolillo S
- Ashish A
- Ashley E
- Ashraf S
- Ashraf S
- Ashton L
- Ashworth M
- Asiimwe IG
- Aslibekyan S
- Asselta R
- Atanasovska B
- Atkinson D
- Atkinson EG
- Attwood B
- Aucella F
- Augustin M
- Auld D
- Auld F
- Austin K
- Austin P
- Auton A
- Auton A
- Avendano-Ortiz J
- Awano N
- Ayers A
- Azarzar S
- Aziz F
- Azuma M
- Azuure C
- Azzolini E
- Baba R
- Baba T
- Bach B
- Bacher P
- Bachetti T
- Badalamenti S
- Badia JR
- Badji RM
- Bahmer T
- Baikady RR
- Baillie JK
- Baillie JK
- Baillie JK
- Baillie JK
- Baines B
- Baines D
- Baines K
- Baird T
- Baird Y
- Bakshi S
- Bakthavatsalam D
- Balaconis MK
- Baldassarri M
- Baldini M
- Ball CA
- Bals R
- Baltzell AH
- Bamford A
- Bamford P
- Banach D
- Banagan J
- Banales JM
- Bancroft H
- Band G
- Bandera A
- Bandini M
- Bandla N
- Bano S
- Baptista D
- Barada O
- Baras A
- Baratti S
- Barber R
- Barbieri C
- Barbieri C
- Barbour A
- Barclay L
- Barclay WS
- Barda B
- Bargagli E
- Bari S
- Barker J
- Barlow G
- Barlow SL
- Barnass S
- Barnes KC
- Baroni S
- Baroni S
- Barreira A
- Barrett F
- Barrett KMS
- Barrett N
- Barron A
- Barry P
- Bartels M
- Bartley S
- Baruah R
- Baselli G
- Bashyal A
- Basikolo C
- Bassetti M
- Bassford C
- Basso MEF
- Bastion V
- Basude S
- Bates H
- Bates M
- Battle C
- Bauchmuller K
- Bax D
- Baxter D
- Baxter N
- Baya N
- Bayo L-A
- Beadle J
- Beadsworth M
- Beale R
- Bean S
- Beaumont K
- Beavis S
- Beck A
- Beckmann ND
- Beech E
- Beech V
- Beekes M
- Beesley K
- Begg C
- Beguin Y
- Behan T
- Beith CM
- Belagodu Z
- Belbin GM
- Belfield H
- Belhaj Y
- Beligni G
- Belisle A
- Bell D
- Bell G
- Bell M
- Bellamy M
- Belli MA
- Bellinghausen C
- Bellini A
- Bellwood R
- Below JE
- Bemand T
- Benetti E
- Benham L
- Bennet D
- Bennett S
- Bentley M
- Benyon S
- Beppu S
- Beranova E
- Bercades G
- Bergan J
- Bergantini L
- Berger MM
- Bergomi M
- Bergomi P
- Berkowitz N
- Bernardo D
- Bernasconi A
- Bernatoniene J
- Berridge J
- Bertrand A
- Best N
- Bettini LR
- Beudel M
- Bevan E
- Bewley J
- Bhardwaj N
- Bhatia N
- Bhatterjee R
- Bhuie P
- Bi R
- Bianchi F
- Bianco C
- Bibert S
- Bibert S
- Bibi F
- Biddle J
- Biesecker L
- Biggs H
- Biondi A
- Birch J
- Birch J
- Birch S
- Birchall K
- Birchall K
- Bird S
- Birkinshaw I
- Birney E
- Birt M
- Biscarini F
- Black E
- Black K
- Blackledge B
- Blackledge B
- Blackman H
- Blakemore H
- Blanco-Grau A
- Blasi F
- Blay N
- Blay N
- Blow S
- Blunt M
- Boada M
- Board S
- Bocciardi R
- Bocciolone M
- Bochud M
- Bochud P-Y
- Bochud PY
- Bochud PY
- Bochud PY
- Bociek A
- Boer C
- Boezen M
- Bogaard HJ
- Bogaert D
- Boillat N
- Boillat-Blanco N
- Bokhari M
- Bolton M
- Bolton R
- Bolze A
- Bombace S
- Bomers M
- Bonfanti P
- Bonner S
- Bonta PI
- Booker L
- Booth L
- Booth S
- Borislavova B
- Borra C
- Bos L
- Bosari S
- Bosio G
- Bosse Y
- Botello A
- Bothma P
- Botta G
- Botta M
- Boua PR
- Bouab M
- Bough L
- Boughton AP
- Boujemla B
- Bouras K
- Boutros P
- Bouysran Y
- Bowes A
- Bowles R
- Boyle P
- Boyle R
- Boz C
- Bradford Y
- Bradley C
- Bradley P
- Bradley-Potts J
- Bradshaw Z
- Brady A
- Brady M
- Brady R
- Brahier T
- Brandwood C
- Branney D
- Brantwood C
- Brassard N
- Braun A
- Braun N
- Brayne A
- Brealey D
- Brealey D
- Breen G
- Bremmer P
- Brennan B
- Brenner B
- Brenner T
- Bretherick AD
- Brett M
- Brett S
- Brickell K
- Bridgett V
- Brimfield L
- Brinkworth E
- Briton K
- Brittain-Long R
- Britvan B
- Bromley M
- Brooke H
- Brooks S
- Brouwer MC
- Brown A
- Brown A
- Brown A
- Brown CW
- Brown E
- Brown J
- Bruce M
- Brunak S
- Bruno R
- Brunton M
- Brusco A
- Bruttini M
- Bryant J
- Bryant S
- Bryant S
- Buckley C
- Buckley S
- Bugiani M
- Bujanda L
- Bulik CM
- Bulle E
- Bullock K
- Bulteel N
- Bunni L
- Burda D
- Burden T
- Burn I
- Burnett C
- Burns K
- Burt K
- Burtenshaw A
- Burtenshaw A
- Burton M
- Busani S
- Busson A
- Bussotti M
- Bustamante C
- Butcher D
- Buti M
- Butler A
- Butler S
- Butler-Laporte G
- Butler-Laporte G
- Butler-Laporte G
- Butler-Laporte G
- Butte MJ
- Butterworth AS
- Butterworth-Cowin N
- Button H
- Buxbaum JD
- Buxbaum JD
- Buxbaum JD
- Byun J
- Caba Llero-Garralda A
- Cabrelli L
- Caceres M
- Cadilla CL
- Cagova L
- Caldarelli GP
- Calderon EJ
- Callaghan M
- Callier S
- Camby S
- Cameli P
- Campbell A
- Campbell H
- Campbell R
- Campbell R
- Campos S
- Camsooksai J
- Canaccini A
- Canakoglu A
- Cantarini L
- Cantor MN
- Capasso M
- Capitani K
- Cappadona C
- Cappelli S
- Capps N
- Carbral-Ortega L
- Cardamone G
- Carella M
- Carey DJ
- Carli D
- Carlucci N
- Carmody M
- Carmody S
- Carnahan M
- Carnero-Montoro E
- Carrabba M
- Carracedo AD
- Carreras Nolla A
- Carreras A
- Carriero ML
- Carson G
- Carter A
- Carter E
- Carter J
- Carter S
- Carungcong J
- Caruth V
- Casey M
- Cass E
- Castano-Vinyals G
- Castelli F
- Castle K
- Castoldi M
- Castori M
- Castro P
- Caswell M
- Catena E
- Caterson J
- Cathcart S
- Catlow L
- Catterall BWA
- Caulfield MJ
- Caulfield MJ
- Cavazza A
- Cawley K
- Cawthron K
- Cazzaniga M
- Cea C
- Cecconi M
- Ceri S
- Ceri S
- Ceriotti F
- Cerny A
- Cerrato L
- Chablani M
- Chadbourn I
- Chadwick D
- Chadwick D
- Chambler D
- Chan G
- Chan R
- Chand M
- Chandler B
- Chang D
- Chang TS
- Chang X
- Chang Y
- Chapman S
- Charles B
- Charlesworth R
- Charney AW
- Charnock R
- Chasse M
- Chassot J
- Chaudhary K
- Chavan S
- Chechi K
- Chee N
- Cheema Y
- Chen H-H
- Cheng N
- Cherian S
- Chernitsov A
- Cherubini A
- Chetam L
- Cheyne C
- Chiba S
- Chihara Y
- Child J
- Childs D
- Chittoor G
- Chiu A
- Cho JH
- Cho K
- Choe K-W
- Choi S
- Chouchane O
- Choudhury Y
- Chowdhury M
- Christle J
- Chubachi S
- Chueca N
- Chukkambotla S
- Chukkambotla S
- Chung R
- Chung W
- Churchhouse C
- Chwialkowska K
- Chwialkowska K
- Ciccarelli M
- Ciesek S
- Cirulli ET
- Claassen S
- Claire W
- Clamp S
- Clapham M
- Claringbould A
- Clarinval M
- Clark A
- Clark JJ
- Clark M
- Clark M
- Clark R
- Clark R
- Clark S
- Clark T
- Clark V
- Clarke D
- Clarke EA
- Clarke N
- Clarkson M
- Clayton S
- Clement I
- Clements S
- Clerc O
- Cloherty A
- Clohisey S
- Clohisey S
- Clohisey S
- Clohisey S
- Coates C
- Cockrell M
- Coetzee S
- Coghlan P
- Coignet M
- Coiro G
- Coker D
- Cole J
- Cole J
- Cole S
- Cole S
- Cole S
- Coleman D
- Coles H
- Colley J
- Collier D
- Collier D
- Colligan G
- Collignon A
- Collignon A
- Collini P
- Collins A
- Collins BL
- Collins C
- Collins E
- Collins E
- Collins K
- Collis M
- Colombo F
- Colombo R
- Combes E
- Conen A
- Connolly K
- Connor M
- Conticini E
- Convery K
- Conyngham J-A
- Cooke GS
- Cooper J
- Cooper L
- Cooper L
- Corcoran E
- Cordero AIH
- Cordioli M
- Cordioli M
- Cordioli M
- Cordioli M
- Cordioli M
- Cordioli M
- Cordioli M
- Cornberg M
- Cornell S
- Cornely OA
- Corral MA
- Correia GDS
- Corridi M
- Cortes B
- Cortes B
- Cosgrove C
- Cosgrove D
- Cosier T
- Cossarizza A
- Costantino G
- Cother N
- Coton Z
- Coulding M
- Coutts A
- Coventry T
- Coviello DA
- Cowley A
- Cowley A
- Cowley N
- Cowton A
- Cox A
- Cox H
- Cox NJ
- Coyle J
- Craig J
- Crawley R
- Creagh-Brown B
- Crew A
- Crickmore V
- CRiPSI
- Crisp N
- Criste K
- Cristiano D
- Croci L
- Croci S
- Croft M
- Crook DW
- Crooks K
- Crotti L
- Crowe R
- Crowley M
- Cruz C
- Cullum L
- Cunningham A
- Cunningham M
- Cupitt J
- Cupitt J
- Curgenven H
- Curtis CJ
- Cusack R
- Cusick C
- Cutino-Moguel M-T
- Cutler S
- D'Acremont V
- D'Alessandro M
- D'Amato M
- D'Angio M
- D'Sylva S
- Da Gloria EF
- Dabe S
- Daga S
- Daglish J
- Dale K
- Dale S
- Dalton J
- Dalton K
- Daly M
- Daly MJ
- Daly Z
- Dalziel J
- Damas JK
- Dance A
- Danesh J
- Daniel A
- Daniel P
- Daniels A
- Darcis G
- Dark P
- Dark P
- Darlington K
- Darwish D
- Dasgin J
- Daubney E
- Davey M
- Davey M
- David B
- David C
- Davidson N
- Davies C
- Davies E
- Davies F
- Davies G
- Davies K
- Davies L
- Davies M
- Davies M
- Davies R
- Davis C
- Davis C
- Davis L
- Davis LK
- Davison C
- Dawson C
- Dawson D
- Dawson J
- Day N
- Daya M
- de Brabander J
- de Bree G
- de Bruin S
- de Cid R
- de Cid R
- de Geus EJC
- de Gordoa LO-R
- de Gordoa LO-R
- De Grandi A
- de Jong H
- de Jong MD
- De la Horra C
- De Neef M
- de Pablo R
- de Rojas I
- de Salazar A
- de Silva T
- De Vivo O
- De Vivo O
- de Vries H
- Deacon B
- Deacon B
- Dearden J
- Death Y
- Deboever C
- Debreceni G
- Deelen P
- Deelen P
- Deery J
- Degenhardt F
- Dei S
- Dela Rosa A
- Delaneau O
- Delgado CC
- Delgado J
- Della Monica M
- Dellot P
- Deloukas P
- Demetriou C
- Denmade C
- Dennis C
- Dent K
- Dent M
- Depante M
- Dervisevic S
- Desanctis E
- Desgranges F
- deSouza F
- Di Angelantonio E
- di Bartolomeo C
- Di Biagio A
- Di Domenico P
- Di Pietro M
- Di Sarno L
- Di Valentin E
- Digby B
- Digby S
- Dincarslan O
- Ding L
- Ding Y
- Djeugam B
- Do R
- Dobano C
- Dobson E
- Docherty AB
- Doddato G
- Dodds S
- Domingues F
- Donaldson A
- Donaldson D
- Donati A
- Dongelmans D
- Donlon S
- Donnachie J
- Donne B
- Donnelly K
- Donnelly L
- Donner K
- Donnison P
- Donnison P
- Donohue C
- Dooks E
- Doonan R
- Dopazo X
- Dore R
- Dormand N
- Douglas K
- Douthwaite S
- Downes C
- Drake TM
- Dreher M
- Drummond A
- Drummond A
- Duberly S
- Dudman S
- Dueker N
- Duffield J
- Duffin D
- Duffy K
- Duffy S
- Duga S
- Duga S
- Duga S
- Dumas M-E
- Duncan E
- Duncan T
- Dunham I
- Dunmore C
- Dunn C
- Dunning J
- DuRand I
- Durand M
- Durga L
- Durham C
- Durie A
- Durrans LJ
- Durrant G
- Dushianthan A
- Duskova M
- Dutta AK
- Dutta AK
- Dutta AK
- Dyer P
- Dyer T
- Dykes J
- Dyrhol-Riise AM
- Eapen B
- Earle SG
- Eastgate-Jackson C
- Easthope A
- Easthope A
- Easthope A
- Easton J
- Ebano P
- Eckbad C
- Edahiro R
- Edmond I
- Edwards M
- Efford G
- Egan J
- Egger T
- Eggermann T
- El Kandoussi K
- Elabd H
- Elbers P
- Elhassan M
- Ellinghaus D
- Elliott A
- Elliott K
- Ellis H
- Elsaadany M
- Elston K
- Eltayeb A
- Emiliozzi A
- Emmert D
- Endo A
- Endo M
- English K
- Enomoto T
- Erard V
- Erard V
- Erdmann J
- Eriguchi Y
- Esko T
- Esmaeeli S
- Espana PP
- Esparza-Gordillo J
- Evans A
- Evans C
- Evitts J
- Ezeobu O
- Eziefula C
- Fabbiani M
- Fadeur M
- Fagan A
- Fairfield CJ
- Falcone M
- Falcone M
- Fallerini C
- Farh K
- Farnell-Ward S
- Farquhar F
- Farre X
- Farre X
- Farzad Z
- Faucon A
- Faucon AB
- Faulkner B
- Faulkner M
- Fava F
- Fave M-J
- Faverio P
- Fawkes A
- Fazaal J
- Fearby M
- Febbo P
- Fegan C
- Feldt T
- Felton T
- Feng Y-CA
- Ferguson S
- Feri M
- Fernandes K
- Fernandes R
- Fernandez J
- Fernandez Z
- Fernandez-Cadenas I
- Fernandez-Cadenas I
- Fernandez-Cadenas I
- Fernandez-Roman J
- Ferrando C
- Ferreira MAR
- Ferrer R
- Ferrero GB
- Ferri C
- Ferrusquia-Acosta J
- Ferwerda B
- FHoGID
- Fidler K
- Filipe ADS
- Filipe H
- Filipovic M
- Filippidis P
- Filshtein-Sonmez T
- Finch C
- Finch L
- Findlay L
- Fine C
- Finer S
- Finer S
- Finernan P
- Finn A
- Finn J
- Finn S
- Finney C
- Finucane H
- Finucane H
- Fiorentino G
- Fisher E
- Fisher LWS
- Flaherty L
- Flanagan R
- Fletcher T
- Fleuren L
- Flint N
- Foco L
- Fofano A
- Folkersen L
- Folkersen L
- Folkes L
- Folseraas T
- Foote D
- Force HCT
- Ford A
- Forgetta V
- Forgetta V
- Forsey M
- Forsey M
- Foster L
- Foster T
- Foti G
- Fotiadis S
- Fottrell-Gould D
- Foucras S
- Fourman MH
- Fourman MH
- Fowler S
- Fowler T
- Fox C
- Fox H
- Fox J
- Fracanzani AL
- Francescatto M
- Francescatto M
- Franchi F
- Francioli L
- Francisci D
- Franke A
- Franke G
- Franke L
- Franke L
- Frankham J
- Frediani B
- Freimer N
- Friaza V
- Friedman P
- Friolet R
- Frippiat F
- Frischknecht M
- Frise M
- Frithiof R
- Frullanti E
- Fuchimoto Y
- Fuchsberger C
- Fuchsberger C
- Fujitani S
- Fujiwara A
- Fuke S
- Fukui T
- Fukunaga K
- Fukuyama S
- Fuller B
- Fullerton D
- Funatsu Y
- Fundin B
- Furini S
- Furlong A
- Furniss J
- Furniss J
- Gabbi C
- Gabrieli A
- Gaddis M
- Gaede KI
- Gales A
- Galimberti D
- Gallagher B
- Gallego-Duran R
- Galvan-Femenia I
- Galvan-Femenia I
- Gamble C
- Ganesan A
- Ganna A
- Ganna A
- Ganna A
- Ganna A
- Garbarino L
- Garcia Sanchez F
- Garcia F
- Garcia SM
- Garcia-Aymerich J
- Garcia-Dorival I
- Garcia-Etxebarria K
- Garcia-Fernandez A-E
- Gardner A
- Garg A
- Garg S
- Garland Z
- Garmendia A
- Garner L
- Garrido Chercoles A
- Garrioch S
- Gascoyne R
- Gass MC
- Gassner C
- Gatti F
- Gay B
- Gaylard J
- Gaylard J
- Gaziano JM
- Gazon H
- Geary T
- Geerlings S
- Geerts B
- Geijtenbeek T
- Gellamucho M
- Gemmell L
- Gendall E
- George A
- George L
- Georges M
- Georges M
- Gerussi A
- Geschwind DH
- Geschwind DH
- Gettler K
- Gharavi AG
- Gherman A
- Ghosh B
- Ghoussaini M
- Giannattasio F
- Gibson S
- Gignoux CR
- Gilbert K
- Gilchrist T
- Giles J
- Giliberti A
- Gill J
- Gill M
- Giorgio E
- Giorli A
- Giot J-B
- Girach R
- Girardis M
- Girbes A
- Giroule F
- Girshick A
- Girvan M
- Gkrania-Klotsas E
- Glasgow S
- Glass L
- Gledhill L
- Glessner JR
- Glueck A
- Goddard W
- Godden J
- Goerg S
- Goff E
- Goffard J-C
- Gofflot S
- Gogele M
- Goikoetxea J
- Golden D
- Golden D
- Golder K
- Golding H
- Goldsmith A
- Goldstein DB
- Goldstein JI
- Golightly A
- Gomez R
- Gomez-Cabrero D
- Gon Y
- Gondo P
- Gonzalez Cejudo T
- Goodchild D
- Goodsell J
- Goodwin E
- Goorhuis B
- Gopal S
- Gordon A
- Gordon E
- Gori A
- Gori M
- Gorman C
- Gorzynski J
- Gountouna E
- Graham C
- Grasselli G
- Grassi D
- Gratrix A
- Grau N
- Grauslyte L
- Green CA
- Green J
- Green RC
- Greenhalf W
- Greenhalf W
- Greer S
- Gregory J
- Greig J
- Griffin D
- Griffin JL
- Griffiths C
- Griffiths CJ
- Griffiths F
- Grimes G
- Grimmer L
- Grimsrud MM
- Grobusch MP
- Grp NS-CS
- Grzymski JJ
- Gualtierotti R
- Guarnaccia A
- Guarnaccia A
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- zu Bentrup FM
- Zucchi P
- Zwinderman AHK
- Zyndorf M
- Publication venue
- Publication date
- 01/01/2021
- Field of study
Get PDFThe genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease
A second update on mapping the human genetic architecture of COVID-19
- Author
- Abd Elghafar MS
- Abdel-Aziz M
- Abdelrazik M
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- Zawadzki P
- Zawati MH
- Zborowski AC
- Zeberg H
- Zechner M
- Zhang Q
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- Zárate RN
- Zúñiga-Ramos J
- Álvarez BG
- Ávila-Arcos MA
- Ávila-Arcos MC
- Özer O
- Überla K
- Þorsteinsdóttir U
- Publication venue
- Nature Research
- Publication date
- 21/06/2023
- Field of study
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