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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.
Abedalthagafi M.
Abel L.
Abernathy C.
Abraheem A.
Abul-Husn N. S.
Acquilini D.
Adams C.
Adams E. L.
Adams K.
Adamsara A.
Adanini O.
Adeleye O.
Adra D.
Afilalo J.
Afilalo M.
Afolabi D.
Afrasiabi Z.
Agasou A.
Agrawal S.
Aguero D.
Ahmad N.
Ahmadi S.
Ahmed A.
Ahmed C.
Akeroyd L.
Akhtar M. N.
Akinkugbe O.
Aksentijevich A.
Al-Afghani H.
Al-Awdah L.
Alaamery M.
Alahmadey Z. Z.
Alaverdian D.
Alavere H.
Albader A.
Albaiceta G. M.
Albakri J. K.
AlBardis H.
Albeladi M.
Albesher N.
Albrich W.
AlDhawi N.
Aldridge J.
Aleagha A. E.
Alexander P.
Alfonso J.
Alghamdi B.
Alghamdi J.
Ali A.
Ali A.
Ali I. A. M.
Ali S.
Aliannejad R.
Aljawini N.
AlJohani S.
Alkwai S.
Allan A.
Allan E.
Allan J.
Alldis Z.
Allen L.
Allen M.
Allen S.
Allibone S.
Allison K. S.
Allos R.
Ally S. M.
AlMalik A.
Almalki F.
Almohammed I.
Almutairi M.
Alotaibi S.
Alowayn A. M.
Alqahtani S.
Alqubaishi F.
Alrashed M.
Alshareef A.
Alsolm E.
Alswailm M.
Altabaibeh A.
Alvaro A.
AlZahrani D.
Amin V.
Amirsavadkouhi A.
Amitrano S.
Anastasescu E.
Anderson F.
Anderson J.
Anderson M.
Anderson P.
Anderson S.
Anderson S.
Anderson T.
Andolfo I.
Andretta F.
Andreucci E.
Andrew A.
Andrew B.
Andrew G.
Andrews E.
Andrews S. J.
Anedda F.
Anemoli V.
Annis A.
Antcliffe D.
Antinori A.
Antoni M. D.
Anumakonda V.
Apetri E.
Aquino M.
Arabi Y. M.
Aravindan L.
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Archer K.
Arden T.
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Publication venue: 'Springer Science and Business Media LLC'
Publication date: 01/01/2022
Field of study

Critical 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

PubliCatt

Archivio istituzionale della ricerca - Università di Modena e Reggio Emilia

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.
Abecasis G.R.
Abedalthagafi M.
Abel L.
Abernathy C.
Abraheem A.
Abul-Husn N.S.
Acquilini D.
Adams C.
Adams E.L.
Adams K.
Adamsara A.
Adanini O.
Adeleye O.
Adra D.
Afilalo J.
Afilalo M.
Afolabi D.
Afrasiabi Z.
Agasou A.
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Publication venue: Springer Science and Business Media LLC
Publication date: 07/07/2022
Field of study

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 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

White Rose Research Online

LA-Net: A multi-task deep network for the segmentation of the left atrium

Author: Bharath A
Boniface G
Chubb H
Mahenthran T
Uslu F
Varela Anjari M
Publication venue: 'Institute of Electrical and Electronics Engineers (IEEE)'
Publication date: 01/01/2021
Field of study

Although atrial fibrillation (AF) is the most common sustained atrial arrhythmia, treatment success for this condition remains suboptimal. Information from magnetic resonance imaging (MRI) has the potential to improve treatment efficacy, but there are currently few automatic tools for the segmentation of the atria in MR images. In the study, we propose a LA-Net, a multi-task network optimised to simultaneously generate left atrial segmentation and edge masks from MRI. LA-Net includes cross attention modules (CAMs) and enhanced decoder modules (EDMs) to purposefully select the most meaningful edge information for segmentation and smoothly incorporate it into segmentation masks at multiple-scales. We evaluate the performance of LA-Net on two MR sequences: late gadolinium enhanced (LGE) atrial MRI and atrial short axis balanced steady state free precession (bSSFP) MRI. LA-Net gives Hausdorff distances of 12.43 mm and Dice scores of 0.92 on the LGE (STACOM 2018) dataset and Hausdorff distances of 17.41 mm and Dice scores of 0.90 on the bSSFP (in-house) dataset without any post-processing, surpassing previously proposed segmentation networks, including U-Net and SEGANet. Our method allows automatic extraction of information about the LA from MR images, which can play an important role in the management of AF patients

Spiral - Imperial College Digital Repository

King's Research Portal

Mapping the human genetic architecture of COVID-19

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Abdullah T.
Abe R.
Abe S.
Abecasis G. R.
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Adachi T.
Adachi Y.
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Aksentijevich A.
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Wrobel N.
Wu Y.
Wulandari R.
Wyllie D. H.
Wynter I.
Xavier K.
Xue X.
Yadav A.
Yagi K.
Yamada M.
Yamada Y.
Yamagata K.
Yamasaki M.
Yang G.
Yang J.
Yang Z.
Yaspan B.
Yasui Y.
Yates B.
Yatomi M.
Ye C.
Yengo L.
Yermakovich D.
Yi X.
Yonekawa A.
Yoon H.
Yoon K. J.
Yoshida K.
Yoshida S.
Yoshida S.
Yoshida T.
Yoshihara T.
Yoshiya K.
Yoshiyama T.
Youlton N.
Young P.
Yun N.
Zak A.
Zaki A.
Zambon M.
Zamikula J.
Zanella A.
Zanella I.
Zanelli G.
Zara F.
Zarate R.
Zborowski A. C.
Zeberg H.
Zechner M.
Zguro K.
Zhai R.
Zhang M.
Zhao J. H.
Zhen J.
Zheng C.
Zheng T.
Zhou W.
Zhu W.
Zitter L.
Zlatopolsky M.
Zoller H.
Zollner S.
Zongo O.
Zucchi P.
Zyndorf M.
Publication venue: 'Springer Science and Business Media LLC'
Publication date: 01/01/2021
Field of study

The 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

Archivio istituzionale della ricerca - Politecnico di Milano

Archivio della ricerca - Università degli studi di Napoli Federico II

Archivio istituzionale della ricerca - Università di Genova

UTUPub

Archivio istituzionale della ricerca - Università di Modena e Reggio Emilia

Archivio istituzionale della ricerca - Università di Padova

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
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Baines B
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Baird T
Baird Y
Bakshi S
Bakthavatsalam D
Balaconis MK
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Baldini M
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Baptista D
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Barbieri C
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Caceres M
Cadilla CL
Cagova L
Caldarelli GP
Calderon EJ
Callaghan M
Callier S
Camby S
Cameli P
Campbell A
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Camsooksai J
Canaccini A
Canakoglu A
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Cantor MN
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Cappadona C
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Poole A
Pooni JS
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Popov I
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Poscente M
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Potoczna D
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Yoshiya K
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Younes SE
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Zoller H
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zu Bentrup FM
Zucchi P
Zwinderman AHK
Zyndorf M
Publication venue
Publication date: 01/01/2021
Field of study

The 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

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University of Bergen

Archivio Istituzionale della Ricerca - Università degli Studi di Pavia

edoc

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ZORA

Apollo (Cambridge)

St George's Online Research Archive

Explore Bristol Research

A second update on mapping the human genetic architecture of COVID-19

Author: Abd Elghafar MS
Abdel-Aziz M
Abdelrazik M
Abdullah MS
Abe R
Abe S
Abel L
Abel L
Abernathy C
Abraham R
Abraheem A
Abu Alragheb BO
Abulail JA
Acklery A
Acosta-Herrera M
Adachi T
Adachi Y
Adam R
Adams C
Adams K
Adams N
Adanini O
Afifi N
Afilalo J
Afilalo M
Afolabi D
Afrasiabi Z
Afset JE
Agasou A
Aghemo A
Agravante K
Agrawal A
Agrawal S
Aguado JM
Aguilar C
Aguilar SEV
Aguilar-Salinas CA
Aguilera-Albesa S
Agüero D
Ahmad HF
Ahmad N
Ahmadhaider N
Ahmed A
Ahmed C
Ahram M
Ai M
Ain Q
Aitkin E
Akeroyd L
Akhtar MN
Akinkugbe O
Al-Ani A
Al-Ja’afreh MM
Al-Kadash A
Al-Kasasbeh MM
Al-Moasseb H
Al-Muftah W
Al-Sarraj Y
Alamer LM
Alasdair F
Alawneh FM
Alawneh LM
Albaiceta GM
Albano G
Albillos A
Albrecht W
Aldridge J
Alexander P
Alfonso J
Alhousani TN
Ali A
Ali HH
Ali IAM
Ali S
Aliberti S
ALjalamdeh M
Allan A
Allan E
Allan J
Alldis Z
Allen L
Allen M
Allen S
Allen U
Allibone S
Allison KS
Allouzy SK
Ally SM
Almadana V
Almaden-Boyle C
Almoguera B
Alpuche-Aranda C
AlRawashdeh TJ
Alsafadi DB
Alshaer W
Alsoub FS
Altabaibeh A
Alvarez N
Alvaro A
Alzuraiqi MR
Amamio M
Aman NF
Amin V
Amiya S
Ampuero J
Anan R
Anastasescu E
Andersen S
Anderson J
Anderson M
Anderson P
Anderson S
Anderson S
Anderson T
Ando A
Andrade V
Andreou P
Andreu-Bernabeu Á
Andrew A
Andrew B
Andrew G
Andrews J
Andrews S
Andrews SJ
Angelini C
Ansari AI
Antcliffe D
Antoine P
Antony S
Anumakonda V
Anwer M
Anzai T
Apetri E
Aquino M
Aquino-Gálvez A
Arai D
Arakelyan A
Arana-Arri E
Arana-Arri E
Arango C
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Arimura K
Armistead J
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Artiga M-J
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Astin-Chamberlain R
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Athanasiou L
Atkinson EG
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Auton A
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Awasthi S
Ayers A
Ayo NI
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Badji RM
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Baikady RR
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Baker M
Bakthavatsalam D
Balaconis MK
Baldini M
Balla D
Bals R
Bamford A
Bamford A
Bamford P
Banach D
Banales JM
Banasik K
Banasik K
Bancroft H
Band G
Bandera A
Bandla N
Bani younis FM
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Butler-Laporte G
Butt F
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Butterworth-Cowin N
Button H
Buttriss C
Caballero-Garralda A
Cabral-Ortega L
Cabrelli L
Cabrero DG
Cadenas IF
Cadilla CL
Cagova L
Cal-Sabater P
Calderón EJ
Calderón EJ
Cale E
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Campbell A
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Campbell S
Campigotto A
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Cantú-Brito C
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Cappadona C
Cappelli C
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Carbonell C
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Cardwell A
Carmody M
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Carnahan M
Carpani R
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Carracedo Á
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Castelao JE
Castillejos-López M
Castoldi M
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Caulfield MJ
Cavallero A
Cavazza A
Cave A
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Cea C
Ceballos FC
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Cejudo TG
Ceriotti F
Cerpa LC
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Chadwick R
Chaliasos K
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Chang D
Chang TS
Chao G
Chapman S
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Cheatley PL
Cheema Y
Chen H-H
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Chercoles AG
Cherian S
Chernitsov A
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Cherubini A
Chesters K
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Cheyne C
Chiba S
Chihara Y
Chikowore P
Childs D
Chiquete E
Chirino-Pérez A
Chirouze C
Chisholm C
Chiu A
Choe K-W
Choudhr O
Choudhury Y
Chowdhary S
Christaki E
Christian MA
Chubachi S
Chueca N
Chuhan NT
Chukkambotla S
Chung M
Churchhouse C
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Chávez-Manzanera E
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Cirulli ET
Citerio G
Claire D-R
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Clark M
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Clark V
Clarke N
Clarkson M
Clausen M
Clayton S
Clement I
Clements S
Coates C
Cobat A
Cochrane P
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Coghlan P
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Conde-Vicente R
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Cookson R
Cooper J
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Cooper L
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Corbetta A
Corcoran E
Corcoran K
Cordero-Lorenzana ML
Cordioli M
Cordioli M
Corin C
Cornberg M
Cornell S
Cornell T
Cornely OA
Corner A
Corral MA
Cortes B
Cortes-Sanchez JL
Corton M
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Cosier T
Costantino G
Cother N
Coto E
Coton Z
Cottam L-J
Cottle J
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Coventry T
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Crew A
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Cruz C
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Cruz-Bautista I
Cruz-Cruz AD
Csabi P
Cuerda VM
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Daly MJ
Daly Z
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DAmato F
Damås JK
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Darcis G
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Darlington K
Darnaude MT
Darnell S
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Dasgin J
Daubney E
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Davidyants M
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De Gordoa LO-R
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De Jesús Suárez López J
De la Horra C
De León-Garduño AP
De los Ángeles Vargas-Martínez M
De Martino-Rodríguez A
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De Pablo R
De Quirós FGB
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De Salazar A
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Degenhardt F
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Del Consuelo Rodríguez Mancilla M
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Diaba C
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Dinh KM
Dixit RD
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Djeugam B
Dobaño C
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Domínguez-Mayoral A
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Ducharme FM
Dudman S
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Fernandez-Cadenas I
Fernandez-Roman J
Fernandez-Ruiz J
Fernández J
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Hernández Cordero AI
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Huang Y-WJ
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Irvine V
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Jaramillo MAMD
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Jensen B-EO
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Jermy B
Jerome E
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Jetha C
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Jimenez-Sousa MA
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Johansson PI
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Joshi CG
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Joshy A
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Julienne H
Julià A
Junaid A
Jung KJ
Juzenas S
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Kadiri S
Kagaya T
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Kajtor I
Kaliappan A
Kallon D
Kalman JL
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Kamata H
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Kamundi C
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Karczewski KJ
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Lorenzo-Salazar JM
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Luchessi AD
Ludwig KU
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Martinez ML
Martinez-Lopez I
Martinez-Nieto O
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Martinez-Resendez MF
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O’Connor D
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Silbiger VN
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Publication venue: Nature Research
Publication date: 21/06/2023
Field of study

Spiral - Imperial College Digital Repository

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GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19

Author: Abdelrazik M
Abedalthagafi M
Abel L
Abel L
Abellan J
Abernathy C
Abraheem A
Acklery A
Acosta-Isaac R
Adam R
Adams C
Adams K
Adams N
Adanini O
Afolabi D
Agasou A
Agravante K
Agravante K
Agrawal S
Aguado JM
Aguilar C
Aguilar PM
Aguilera-Albesa S
Ahmad N
Ahmadhaider N
Ahmed A
Ahmed C
Aitkin E
Akeroyd L
Akhtar MN
Akinkugbe O
Al-Moasseb H
Alasdair F
Alba J
Albu S
Alcalá-Gallardo KAM
Alcoba-Florez J
Aldridge J
Alex B
Alexander P
Alfonso J
Algarin-Lara HR
Ali A
Ali HH
Ali IAM
Ali S
Allan A
Allan E
Allan J
Alldis Z
Allen L
Allen M
Allen S
Allibone S
Allison KS
Ally SM
Almadana V
Almaden-Boyle C
Almeida J
Almoguera B
Alonso MR
Altabaibeh A
Alvarez N
Alvaro A
Alves MDM
Amamio M
Amamio M
Amin V
Anastasescu E
Anderson J
Anderson M
Anderson P
Anderson S
Anderson S
Anderson T
Andreou P
Andreu-Bernabeu Á
Andrew A
Andrew B
Andrew G
Andrews J
Andrikopoulos P
Antcliffe D
Antoine P
Antonijoan MR
Antony S
Anumakonda V
Anwer M
Apetri E
Aquino M
Arana-Arri E
Aranda C
Arango C
Araque C
Araujo IMT
Araujo NK
Aravindan L
Arbane G
Arcanjo AC
Archer K
Arden T
Arias SS
Arif S
Armistead J
Armstrong D
Armstrong L
Armstrong R
Arnaiz A
Arnott A
Arora M
Arranz MJ
Artiga M-J
Ashby K
Ashok SR
Ashraf S
Ashton L
Aslibekyan S
Astin-Chamberlain R
Atayeva N
Attwood B
Atwal I
Auld F
Austin K
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Auton A
Avello-Malaver Y
Ayers A
Ayuso C
Bach B
Badal B
Baddeley A
Bafitis V
Baikady RR
Bailey L
Baillie JK
Baillie JK
Baillie K
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Baird T
Baird Y
Baker M
Bakthavatsalam D
Baldión-Elorza AM
Bamford A
Bamford A
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Baptista-Rosas RC
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Barclay WS
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Barrera-Penagos V
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Baruah R
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Basikolo C
Bastion V
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Bayo L-A
Beadle J
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Beasley A
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Belhassen-Garcia M
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Blackledge B
Blackledge B
Blackman H
Blakemore H
Blanca-López N
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Bland Y
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Bradshaw Z
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Bridgett V
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Brochado-Kith Ó
Bromley M
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Brown CW
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Brugada R
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Cinquina Z
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Clarey E
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Clark V
Clarke N
Clarkson M
Clayton S
Clement I
Clements S
Clohisey S
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Collins V
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Conejo IP
Connell J
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Conyngham J-A
Cooke GS
Cookson R
Cooper J
Cooper L
Cooper L
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Cordero-Lorenzana ML
Corella D
Corin C
Cornell S
Cornell T
Corner A
Corral MA
Corrales A
Cortes-Sanchez JL
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Cosier T
Costa TX
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Coton Z
Cottam L-J
Cottle J
Coulding M
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da Silva Filipe A
da Silva GV
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Darnaude MT
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de Quirós FGB
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de Sousa Alves Neri JL
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Fuentes CS
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Furlong A
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Gadea I
Gagliardi L
Gago-Domínguez M
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Gallo JPV
Galoppo C
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Garcia-Cerrada C
Garcia-García J
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
Gardner A
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Gascoyne R
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Gemmell L
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Glasgow S
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Gnanapragasam P
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Gonzalez-Sagrado M
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Granados EL
Gratrix A
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Grauslyte L
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Guegel GP
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Gutiérrez-Bautista JF
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Harford R
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Harling R
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Harvey A
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Hastings J
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Hayman M
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Headlam E
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Helm D
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Herdman-Grant R
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Hernandez-Ortega LD
Hernández-Pérez G
Hernández-Vaquero R
Heron AE
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Herranz MT
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Herrero MJ
Herrero-Gonzalez A
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Hilltout P
Hilton M
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Hinds C
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Hitchcock R
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Hodgkiss T
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Holding K
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Horcajada JP
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Huang Y-WJ
Hubbard K
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Huffenberger A
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Imeson-Wood J
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Inweregbu K
Ireland J
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Irvine V
Ishaq T
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Jackman S
Jackson C
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Jackson P
Jackson S
Jackson Y
Jackson-Lawrence K
Jacob R
Jacomo RH
Jacques N
Jain K
Jain S
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Jamieson A
Jara R
Jardine C
Jarmain J
Jarman C
Javaid A
Jazmin PM
Jefferson P
Jeffrey H
Jenkins S
Jenkins S
Jennings C
Jepson E
Jerome E
Jerry D
Jetha C
Jha R
Jhanji S
Jimenez-Sousa MA
Jiménez P
Jiménez Á
Jiménez-Alfaro I
Jobes L
Joefield T
John L
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Johnson E
Johnson L
Johnson R
Johnston B
Jones C
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Jones E
Jones F
Jones GAL
Jones H
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Jones K
Jones M
Jones O
Jones R
Jones S
Jones TO
Jordan I
Jose S
Jose S
Joseph A
Joseph R
Joseph S
Joshy A
Joy R
Jude E
Kadiri S
Kajtor I
Kaliappan A
Kallon D
Kamal L
Kamangu B
Kamath P
Kamundi C
Kannan T
Kanu R
Kapoor R
Karthik K
Kasipandian V
Kassam J
Katary A
Kaul S
Kausar R
Kavanagh L
Kay A
Kayani A
Kaye C
Kaye D
Kazi A
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Keating L
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Keating S
Keenan N
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Keith S
Kelly C
Kelly D
Kelly F
Kelly S
Kelly-Baxter M
Kelsall O
Kennard-Holden G
Kennedy-Hay S
Kent A
Kent H
Kent M
Keshet-Price J
Khade R
Khalifeh Z
Khaliq W
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Khan M
Khera J
Khoo S
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Kilroy S
Kinch A
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King C
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Kirkby A
Kitching A
Kitson R
Klaric L
Klenerman P
Knight A
Knight J
Knight S
Knight SR
Knighton A
Knights E
Knowles K
Kolakaluri L
Kong T
Kosifidou E
Kousathanas A
Krishnamurthy V
Kubisz-Pudelko A
Kumar R
Kumar S
Kupiec K
Kuravi A
Laguna-Goya R
Laha S
Lahnsteiner E
Lake V
Lamb T
Lamond Z
Lancaster N
Lancoma-Malcolm I
Landeg B
Langley M
Langridge E
Langton H
Laorden D
Lapunzina P
Lapunzina P
Larman G
Lasa-Lazaro M
Latham S
Latif M
Lattig MC
Lauder C
Lauriente A
Law A
Law A
Law D
Law R
Law S
Lawton T
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Leaver S
Ledgard C
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Lee S
Leeming G
Lees R
Leggett S
Leigh M
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Leonard B
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León SR
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Lidstone-Scott R
Liew J
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Lim WS
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Linfield-Brown G
Ling L
Lingeswaran S
Linnett V
Lisboa A
List A
Little J
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Lloyd G
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London E
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Loosley R
Lopez JRA
Lopez-Garcia E
Lopez-Rodriguez R
Lorah S
Lorente L
Lorusso R
Love N
Loveridge A
Low E
Lozano JE
Lozano-Espinosa M
Lubimbi G
Lucas R
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Lye A
Lyle A
Lynch C
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Lyons C
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López-Ruz MA
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Mac A
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MacGoey P
Macharia I
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Mackintosh K
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Macías EM
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Maizcordoba M
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Male M
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Malinauskas T
Mallinson J
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Mancebo E
Manley R
Manna S
Manso K
Mapfunde I
Maqsood Z
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Marriott X
Marsden T
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Martin-Fernandez M
Martin-Pedraza L
Martindale T
Martinez A
Martinez ML
Martinez-Lopez I
Martinez-Nieto O
Martinez-Paz P
Martinez-Perez A
Martinez-Resendez MF
Martins L
Martinson V
Martir G
Martín BB
Martín MD
Martín MM
Martín V
Martín-López C
Martín-Oterino J-Á
Martín-Vicente M
Martínez JJ
Martínez R
Martínez S
Martínez YF
Martínez-Aquino E
Martínez-González Ó
Martínez-Ramas A
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Matheson J
Mathew B
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McKenna E
McKie H
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Mclean KA
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McMaster E
McMorrow L
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Medeiros JFP
Medeiros KA
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Meijome XM
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Melia D
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Mercado-Sesma AR
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Metryka A
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Moore F
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Moore LSP
Moore SC
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Moraes VMS
Morano EMH
Moreira-Escriche P
Morelos-Arnedo X
Moreno R
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Moreno-Docón A
Moreno-Escalante J
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Motherwell N
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Nikitas N
Nilo AC
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Olivera MR
Olufuwa O
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Openshaw PJM
Orfao A
Origlia GGS
Orlikowska I
Ortega L
Ortega-Paino E
Ortiz-Flores F
Ortiz-Lopez R
Osagie A
Osbourne W
Ostermann M
Otahal I
Otahal I
Otahal I
Otahal I
Oteo JA
Owen S
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Oziegb M
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O’Brien P
O’Brien R
O’Connell S
O’Connell S
O’Connor D
O’Connor G
O’Donohoe L
O’Hara M
O’Hare M
O’Malley L
O’Neil P
O’Neill A
O’Neill L
O’Reilly K
O’Sullivan S
Pachajoa H
Pacheco M
Pacheco-Miranda FJ
Packham S
Padden G
Page V
Paine S
Pairo-Castineira E
Pajak S
Pakou G
Palmarini M
Palmieri C
Pan J
Panadero-Fajardo S
Panteli M
Pappa E
Pappachan N
Paques K
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Pardo MR
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Pariente-Rodríguez R
Paripoorani D
Park L
Parker N
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Parker R
Parkin J
Parkinson N
Parmar C
Parra EJ
Parris V
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Parsons P
Partridge R
Passmore H
Patel A
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Patel M
Patel R
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Paterson T
Pathan N
Patience D
Patil A
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Pawley C
Paxton WA
Payne C
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Pearn C
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Pearson S
Peasgood E
Peces-Barba G
Pedromingo Kus MS
Penacerrada M
Pendlebury J
Penn R
Perales C
Pereira AC
Perez J
Perez P
Perez-de-Nanclares G
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Peterkin Z
Peters C
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Pheby J
Philbin J
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Phillips P
Phipps J
Phull M-K
Pichardo LA
Pickard A
Piercy C
Pinho SMT
Pinnell J
Pinsach-Abuin ML
Pinzuti I
Pinzón LA
Pippard L
Pirie S
Pita G
Pitt A
Pitts S
Pius R
Pla-Junca F
Place M
Planas-Serra L
Player B
Player J
Player J
Plotkin D
Pogreban T
Pogson D
Polgar O
Polgarova P
Pollakis G
Pompa-Mera EN
Ponting CP
Poole A
Poole M
Pope R
Popescu M
Porras MS
Porras-Hurtado GL
Postovalova E
Pothecary C
Pothecary C
Potla D
Potoczna D
Potts K
Poulaka M
Poultney U
Prados MCS
Prady H
Prager K
Pratley A
Prendergast C
Prentice L
Preston S
Price A
Price C
Price N
Price R
Priestley V
Prime Z
Pristopan V
Pritchard K
Pritchard L
Proudfoot N
Prout R
Pryce J
Prysyazhna O
Pugh R
Pujol A
Puras FS
Purewal B
Purewal M
Purnell R
Purohit D
Purvis S
Puxty A
Puxty K
Pye K
Pérez C
Pérez-García F
Pérez-Matute P
Pérez-Serra A
Pérez-Tomás ME
Qi T
Qiu X
Quaid S
Quijada MA
Quinn A
Quinn C
Quinn H
Quintela I
Rad L
Radford E
Radhakrishnan J
Rai S
Raith E
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Raithatha A
Raj M
Ralph K
Raman KP
Rambaut A
Ramirez-Montaño D
Ramos H
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Ramsay B
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Ratcliffe J
Ratnakumar A
Ratnam V
Rattray A
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Ray S
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Readion G
Real JS
Recalde D
Recio-Fernández E
Reddy A
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Redondo JS
Reece-Anthony R
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Rees A
Rees J
Rees S
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Resino S
Revill A
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Rivadeneira-Chamorro CS
Rivers V
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Roberts A
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Robinson M
Robinson P
Robles VM
Roche L
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Roche L
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Rodden N
Rodriguez MJ
Rodriguez-Artalejo F
Rodriguez-Gallego C
Rodriguez-Garcia JA
Rodriguez-Hernandez MA
Rodriguez-Nicolas A
Rodriguez-Palmero A
Rodriguez-Urrego PA
Rodríguez-Ferrer M
Rodríguez-Ruiz E
Roe N
Rogers N
Rogers P
Rogerson K
Rohit K
Rojas-Martinez A
Rojo F
Rojo R
Romero-Coronado A
Rooney K
Rooney L
Roper A
Rosa LS
Rosales-Castillo A
Rosaroso L
Rose A
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Rostron A
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Rowan K
Rowland-Jones S
Roy A
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Rubio C
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Ruiz M
Ruiz-Cabello F
Ruiz-Casares E
Ruiz-Cubillan JJ
Ruiz-Hornillos J
Runciman N
Russell CD
Russell CD
Rutherford C
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Ryu J
Saad S
Sabbagh AA
Sacristán ÁG
Saha R
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Saha S
Sainsbury H
Saint B
Salada S
Salamanca HD
Salazar-García L
Salberg A
Salciute E
Saleem M
Salmi S
Salmon K
Salutous D
Saluzzio RP
Samakomva T
Sampson J
Sanabria GME
Sanchez-Rodriguez A
Sancho-Sainz C
Sancho-Shimizu V
Sande E
Sanders J
Sanderson A
Sandhar R
Sandhu R
Sands C
Sangil A
Sangombe M
Santos A
Santos NPC
Sarathy V
Sargeant J
Sathe S
Saunderson A
Saunderson P
Savage F
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Saviciute E
Savill H
Sayan A
Scanlon J
Scherewode J
Schlüter A
Scholefield B
Schon K
Schumacher N
Scott C
Scott JT
Scott L
Scott T
Scott Z
Scott-Brown J
Scriven J
Scriven J
Scriven J
Seaman B
Sedes PR
Segovia S
Segura CC
Sell C
Sellick K
Selvanayagam S
Semple G
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Senaratne D
Serra-Llovich A
Serrano-Ruiz A
Service J
Shafique H
Shah N
Shaikh F
Shankar-Hari M
Shankar-Hari M
Shankar-Hari M
Shanmugasundaram P
Sharland E
Shastri AJ
Shaw CA
Shaw D
Shaw J
Shaw L
Shaw R
Shelley B
Shelton JF
Shelton S
Shepardson S
Shepherd A
Shepperson A
Shiel J
Shiel R
Ship L
Shokkar R
Shoremekun A
Short A
Short S
Shorter S
Shovelton C
Shuker K
Sibbett L
Sicat C
Sicolo MA
Sidall E
Sigfrid L
Silbiger VN
Silva FTC
Silva NS
Silva P
Sim M
Simms R
Simpson K
Simpson S
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Sims T
Sinclair S
Sinfield E
Singh J
Singler K
Singleton J
Singleton J
Sitonik M
Skinner D
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Skyes D
Slack L
Slater V
Slaughter M
Slawson N
Slevin K
Sloan B
Sloane G
Smalira A
Smallwood A
Smeaton J
Smeaton J
Smedley C
Smith C
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Smithson E
Smuts S
Smyth D
Smythe M
Sollesta K
Solomon T
Solé-Violán J
Soria JM
Sorlí JV
Sousa RR
Souto JC
Souza KSC
Souza VS
Speight A
Speirs S
Spencer K
Spencer RG
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Publication venue: Springer Nature
Publication date: 17/05/2023
Field of study

Data 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)

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