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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.
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.
Arbane G.
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

Multi-gene testing in neurological disorders showed an improved diagnostic yield: data from over 1000 Indian patients

Background Neurological disorders are clinically heterogeneous group of disorders and are major causes of disability and death. Several of these disorders are caused due to genetic aberration. A precise and confirmatory diagnosis in the patients in a timely manner is essential for appropriate therapeutic and management strategies. Due to the complexity of the clinical presentations across various neurological disorders, arriving at an accurate diagnosis remains a challenge. Methods We sequenced 1012 unrelated patients from India with suspected neurological disorders, using TruSight One panel. Genetic variations were identified using the Strand NGS software and interpreted using the StrandOmics platform. Results We were able to detect mutations in 197 genes in 405 (40%) cases and 178 mutations were novel. The highest diagnostic rate was observed among patients with muscular dystrophy (64%) followed by leukodystrophy and ataxia (43%, each). In our cohort, 26% of the patients who received definitive diagnosis were primarily referred with complex neurological phenotypes with no suggestive diagnosis. In terms of mutations types, 62.8% were truncating and in addition, 13.4% were structural variants, which are also likely to cause loss of function. Conclusion In our study, we observed an improved performance of multi-gene panel testing, with an overall diagnostic yield of 40%. Furthermore, we show that NGS (next-generation sequencing)-based testing is comprehensive and can detect all types of variants including structural variants. It can be considered as a single-platform genetic test for neurological disorders that can provide a swift and definitive diagnosis in a cost-effective manner

Open Access Repository of IISc Research Publications

Mapping the human genetic architecture of COVID-19

Author: Abdelrazik M.
Abdullah T.
Abe R.
Abe S.
Abecasis G. R.
Abel L.
Abernathy C.
Abraheem A.
Abul-Husn N. S.
Acosta-Herrera M.
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 J. E.
Agasou A.
Aghemo A.
Agranoff D.
Agrawal S.
Aguirre L. A.
Agwuh K.
Ahmad H. F.
Ahmad N.
Ahmed A.
Ahmed C.
Ahmed K. A.
Ai M.
Ail D.
Akeroyd L.
Akhtar M. N.
Akhtar S.
Akinkugbe O.
Aksentijevich A.
Al Thani A.
Al-Muftah W.
Al-Sarraj Y.
Alarcon C.
Alarcon-Riquelme M. E.
Alasdair F.
Alaverdian D.
Alavere H.
Albertos R.
Albillos A.
Albrecht W.
Albrich W.
Albrich W. C.
Aldera E. L.
Aldridge J.
Alegria A.
Alex B.
Alexander P.
Alfonso J.
Algera A. G.
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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 della Ricerca - Università degli Studi di Siena

Archivio istituzionale della ricerca - Alma Mater Studiorum Università di Bologna

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

Seagrass collapse due to synergistic stressors is not anticipated by phenological changes

Author: A Gera
A Moshe
A Nishizawa-Yokoi
A Rotini
AC Bockelmann
AF Zuur
AR Hughes
AWD Larkum
B Munkes
BD Griffen
BD Russell
C Boettiger
C Lauritano
CL Andersen
CM Crain
CT Perry
D Huang
DA Bulthuis
DI Walker
DR Bellwood
E Dattolo
E Dattolo
Emanuela Dattolo
Fabio Bulleri
FL Booker
FT Short
G Pergent
G Roca
Gabriele Procaccini
Gabriella La Manna
Giulia Ceccherelli
IA Serra
Isabel Barrote
J Borum
J Carpenter
J Terrados
J Vandesompele
JM Burkholder
JM Ruíz
João Silva
JW Fourqurean
K McMahon
KL Heck
L Marín-Guirao
L Migliore
L Piazzi
L Tamburello
L Telesca
Lazaro Marin-Guirao
LJ Falkenberg
LL Govers
Luigi Piazzi
M Ashraf
M Costa
M Holmer
M Manzanera
M Montefalcone
M Waycott
ML Pace
MM Katwijk Van
Monya M. Costa
MS Fonseca
MS Fonseca
MS Frederiksen
N Marbà
N Marbá
O Delgado
P Prado
Paola Gennaro
PI Macreadie
PLA Erftemeijer
R Costanza
R Danovaro
R Garcia
R Mittler
R Re
RH Lindeman
RJ Orth
RJ Orth
RKF Unsworth
Roberto Gallia
S Cabaço
S Cabaço
S Giakoumi
S Gobert
S Mazzuca
S Oliva
Silvia Oliva
SL Williams
SM Adams
Stefania Pinna
T Alcoverro
T Garcìa-Sanz
TG Whitham
U Gromping
WN Venables
Publication venue: 'Springer Science and Business Media LLC'
Publication date
Field of study

Crossref

Phenolic profile and antioxidant capacity of Pithecellobium dulce (Roxb) Benth: a review

Author: A Adeniyi
A Altemimi
A Arceusz
A Ashraf
A Biochem
A Khoddami
A Kuri-García
A Mediani
A Mokrani
A Porras-Loaiza
A Suganthi
A Szajdek
A Wall-Medrano
A Wojdyło
AJ Alonso-Castro
AT Valduga
B Fuchs
B Nayak
BG Rao
BM Bachir
BM Khan
C Augusto
C Lee
C Tanase
CD Stalikas
CVK Reddy
D Bhati
D Kadam
DM Nagmoti
DM Nagmoti
F Que
FA Rahman Nur
FI Jibril
G López-Angulo
GN Rao
GN Rao
HN Rajha
HV Annegowda
IFF Benzie
ISC Sulaiman
J Cheema
J Dai
J Kim
J Kubola
J Megala
J Xu
J-H Han
JF Pío-León
K Ojha
K Raju
K Thaipong
K Tzima
KM Schaich
KV Kulkarni
L Qiu
M Alothman
M Gallegos-Zurita
M Kivilompolo
M Krishnaveni
M Kumar
M Lewoyehu
M Pinelo
M Sandahl
M Sugumaran
M Sugumaran
MM De Souza
N Elboughdiri
NC Predescu
NE Kafkas
P Manna
P Ponmozhi
PB Pal
PR Sivakumar
R Amorati
R Apak
R Kalavani
R Lucas-González
R Mccullum
R Monroy
RL Prior
S Chutipaijit
S Karaman
S Kumari
S Preethi
SB Kedare
SD Katekhaye
SK Khanzada
T Le Pham
T Poongodi
U Złotek
V Vanitha
VM Moo-huchin
W Samee
WP Rezende
X Cong-Cong
Z Akar
Z Drinić
Z Gunel
Z Li
Publication venue: 'Springer Science and Business Media LLC'
Publication date
Field of study

Crossref

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

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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
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Anderson P
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Ando A
Andrade V
Andreou P
Andreu-Bernabeu Á
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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
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Arango C
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Arranz MJ
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Artiga M-J
Arumugam P
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Yeung RSM
Yi X
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Yoshida S
Yoshida S
Yoshida T
Yoshihara T
Yoshiya K
Yoshiyama T
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Yue F
Yun N
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Yáñez Z
Zainulabid UA
Zainy T
Zak A
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Zamudio IPM
Zanella A
Zapata-Contreras D
Zapatamartinez M
Zarate R
Zarei N
Zavaleta DAF
Zawadzki P
Zawati MH
Zborowski AC
Zeberg H
Zechner M
Zhang Q
Zhao X
Zheng C
Zheng T
Zhlawi HJ
Zhlawi MWJ
Zholdybayeva E
Zhou W
Zhu W
Zitter L
Zoller H
Zongo O
Zorloni C
Zuñiga-Pacheco P
Zárate RN
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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

Spiral - Imperial College Digital Repository

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
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Baird T
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Bakshi S
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Balaconis MK
Baldassarri M
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Ball CA
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Band G
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Barada O
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Bettini LR
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Bevan E
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Bhatia N
Bhatterjee R
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Blakemore H
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Blow S
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Boada M
Board S
Bocciardi R
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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
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Bolze A
Bombace S
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Bonta PI
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Borislavova B
Borra C
Bos L
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Bosse Y
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Botta G
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Boua PR
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Boughton AP
Boujemla B
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Bowes A
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Bradshaw Z
Brady A
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Brady R
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Brayne A
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Bremmer P
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Bretherick AD
Brett M
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Brickell K
Bridgett V
Brimfield L
Brinkworth E
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Britvan B
Bromley M
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Brooks S
Brouwer MC
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Brown CW
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Bruce M
Brunak S
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Brunton M
Brusco A
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Bryant J
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Buckley C
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Bujanda L
Bulik CM
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Burn I
Burnett C
Burns K
Burt K
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Burton M
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Busson A
Bussotti M
Bustamante C
Butcher D
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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
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Coiro G
Coker D
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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
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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
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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
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Foster L
Foster T
Foti G
Fotiadis S
Fottrell-Gould D
Foucras S
Fourman MH
Fourman MH
Fowler S
Fowler T
Fox C
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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
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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
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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
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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
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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
Gudbjartsson DF
Gude ET
Guerin J
Guerrero JM
Guerrini S
Guery B
Guidelli L
Guillet A
Guindo-Martinez M
Guiot J
Gulati A
Gumbrill B
Gummadi M
Gunning P
Guntz J
Gupta A
Gupta R
Gupta RK
Gurasashvili J
Gurr L
Gustad LT
Gutierrez-Stampa MA
Guturu H
Guyat-Jacques C
Guzman C
Hadebe B
Haefliger D
Hafezi K
Hafkamp F
Hagens L
Haider S
Hairsine B
Hakonarson H
Haldeos A
Hales D
Haley C
Halkes M
Hall K
Halls R
Halpin S
Ham SY
Hamann J
Hambrook G
Hamidi Z
Hamilton D
Hamilton DO
Hammer C
Hammerton K
Hammond N
Han C
Han Y
Hanley S
Hanratty H
Hanses F
Hanson H
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Hao K
Haq R
Hara R
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Hard K
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Harding P
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Hardy E
Hardy J
Harford R
Hargreaves J
Harling R
Harper R
Harrington K
Harris C
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Harris N
Harris V
Harrison A
Harrison A
Harrison D
Harrison EM
Harrison J
Harrison L
Harrison W
Harry E
Hartley C
Hartley J
Hartridge P
Hartshorn S
Harvey A
Harvey D
Hase I
Hasegawa N
Hasegawa T
Hasegawa Y
Hashiguchi M
Hashimoto N
Hashimoto S
Hashino T
Hass I
Hatton J
Havalda P
Hawcutt D
Hawcutt DB
Hawes J
Hayashi K
Hayashi R
Hayashi S
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Hayman M
Hays C
Hayward C
Hazelton T
Heeney E
Heggelund L
Hehr U
Heidecker B
Heilmann-Heimbach S
Helbig ET
Helm D
Hemke R
Hemmrich-Stanisak G
Henderson S
Hendry R
Hendry R
Henket M
Henry D
Hensen K
Herdman-Grant R
Hermans SM
Hernandez Quero J
Hernandez I
Hernandez-Tejero M
Heron AE
Herr C
Herrmann S
Hershman S
Hesseldon L
Heunks L
Hewitt C
Hey S
Heyckendorf J
Hibbert M
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Hierons S
Hiester LL
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Hiki M
Hill H
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Hilldrith A
Hilltout P
Hilton M
Hindale J
Hinds C
Hinney A
Hirai Y
Hirano T
Hirata H
Hiscox JA
Hizawa N
Ho AYW
Ho Y-L
Hobden G
Hobrok M
Hobrok M
Hod E
Hodgkiss T
Hodgson L
Hodgson L
Hoff DAL
Hoffmann P
Hoggart C
Holcombe H
Holding K
Holdroyd K
Holland M
Hollmann M
Holm H
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Holten AR
Holter JC
Home M
Honda T
Hong EL
Hope D
Hope S
Hopkins B
Horby PW
Hormis A
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Horn J
Horner D
Hornsby J
Horowitz JE
Horsley E
Hottenga JJ
Houlden H
Housley K
Houston G
Hov JR
Hovius JW
Howard K
Howe GS
Howie L
Howle R
Howlett A
Hruska M
Hu C
Huang C
Huang QQ
Huang QQ
Huang Y
Huckins LM
Hudig L
Hudson A
Huffman JE
Hughes A
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Hugli O
Hull R
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Humphrey C
Hunkapiller J
Hunt J
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Hunt KA
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Hurt WJ
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Hutton P
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Iacomino M
Ichikado K
Ichimura N
Ihara S
III RJM
Ijaz S
Ikemura S
Ilinsky V
Illig T
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Imamura T
Imaz Ayo N
Imeson-Wood J
Imoto S
Inchingolo G
Ingham J
Initiative CHG
Inomata M
Inoue T
Inoue Y
Intxausti M
Invernizzi P
Inweregbu K
Ioannidis A
Iolascon A
Ionita-Laza I
Iou-Olivgeris MP
Ireland J
Irvine V
Ishaq T
Ishiguro T
Ishihara S
Ishihara S
Ishii M
Ishii T
Ishikawa M
Ishikura H
Islam K
Ismail SI
Isogai S
Isono T
Itan Y
Ito A
Ito F
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Iuso N
Iwagoe H
Izquierdo-Sanchez L
Izumi N
Izumo T
Jackson C
Jackson M
Jackson P
Jackson Y
Jackson-Lawrence K
Jacob R
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Jadot L
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Jakkula S
Jang HY
Jang YR
Jannes CE
Jansen P
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Javaid A
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Jennings C
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Jensen B-EO
Jensen RL
Jeong H
Jerome E
Jetha C
Jha R
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Jhanji S
Jimenez D
Jimenez-Morales D
Joefield T
Johnson E
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Jones TO
Jones TR
Joo E-J
Jordan DM
Jose S
Joseph A
Joseph R
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Joshi R
Josse C
Josyula NS
Joubert P
Joy R
Jude E
Julia A
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Justice AE
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Kamundi C
Kanai M
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Kanda H
Kanehiro A
Kaneyama Y
Kang CK
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Karczewski KJ
Karim MA
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Karina B
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Khoo S
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Kildal AB
Kim A
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Kim JY
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Kimchi N
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Kirkby A
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Kitagawa Y
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Kumanogoh A
Kumar R
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Latiano A
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Ludwig KU
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Mankregod R
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Manuel O
Mapfunde I
Maqsood Z
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Marina Montalban-Hernandez K
Marotti M
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Martins LGDA
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Mclean KA
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Migeotte I
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Mikami Y
Milani C
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Milner L
Minano JIE
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Minica C
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Mitchelmore O
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Miyazaki Y
Miyazawa N
Mni M
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Moermans C
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Mok Q
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Monnery S
Montagnani F
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Moon J
Moore E
Moore F
Moore KHS
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Moore SC
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Moreno-Estrada A
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Nicol L
Niemi MEK
Niemi MEK
Niemi MEK
Niemi MEK
Niemi MEK
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Nikitas N
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Novis C
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Packham S
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Pagani JL
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Page VJ
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Pairo-Castineira E
Pais M
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Panchatsharam S
Pancrazi A
Panese S
Pantet O
Papakonstantinou D
Papineni P
Pappa E
Paraboschi EM
Paraiso H
Paramsothy R
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Parikh V
Parisi SG
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Park KU
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Park WB
Parker R
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Parkinson N
Parkinson N
Parkinson P
Parmar C
Parravicini P
Parris V
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Parsons P
Partha R
Partridge R
Parzibut G
Pasaniuc B
Pasaniuc B
Pascual-Iglesias A
Pasko D
Pasko D
Pasko D
Passmore H
Patel A
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Patel BV
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Paxton WA
Pazos MDLM
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Peculis R
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Pendergrass S
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Penrice-Randal R
Pepperell J
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Perumal S
Peschuck A
Pesenti A
Pessina G
Pestana D
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Peter W
Peters C
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Peterson P
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Pink I
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Pinnell J
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Pintus S
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Piscopo C
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Pogreban T
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Polgar O
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Polikowsky HG
Polimanti R
Pollakis G
Pollard R
Poller W
Pontali E
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Pooni JS
Popescu M
Popov I
Porteous DJ
Portopena L
Poscente M
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Post F
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Pothecary C
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Potla D
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Poultney U
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Pramstaller P
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Prati D
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RegCOVID
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Reilly MP
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Sebra RP
Sedaghati-Khayat B
Seed C
Segala FV
Segala FV
Seilmaier MJ
Sekikawa Y
Sell C
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Selvanayagam S
Semple G
Semple MG
Semple MG
Senaratne D
Sengupta S
Seo K
Seok W
SeroCOVID
Serrano-Ruiz A
Shah A
Shah N
Shang N
Shankar-Hari M
Shankar-Hari M
Shankar-Hari M
Shanmuga P
Shanmugasundaram P
Sharma A
Shastri AJ
Shaw CA
Shaw D
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Shaw V
Shaw VE
Shawcross A
Shears RK
Shelley B
Shelton JF
Shelton S
Shen X
Shepardson S
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Shibata Y
Shibusawa T
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Shirai Y
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Shokkar R
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Sicat C
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Sigfrid L
Silva P
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Sin DD
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Sipeky C
Sivanadhan I
Sizer J
Skinner D
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Spinner CD
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zu Bentrup FM
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Zwinderman AHK
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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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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
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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
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Armistead J
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Ruiz-Cabello F
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Ruiz-Cubillan JJ
Ruiz-Hornillos J
Runciman N
Russell CD
Russell CD
Rutherford C
Rutherfurd C
Ryan L
Ryan P
Ryan-Smith J
Ryu J
Saad S
Sabbagh AA
Sacristán ÁG
Saha R
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Saha S
Sainsbury H
Saint B
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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
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Santos A
Santos NPC
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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
Simpson S
Sims T
Sinclair S
Sinfield E
Singh J
Singler K
Singleton J
Singleton J
Sitonik M
Skinner D
Skinner D
Skyes D
Slack L
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Soria JM
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Sousa RR
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Stead R
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Stevenson L
Stewart K
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Sánchez López AJ
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T-Michael H
Taboada-Fraga X
Tagliavini E
Tait S
Takats Z
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Thomas A
Thomas A
Thomas B
Thomas E
Thomas H
Thomas J
Thomas K
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Thomas V
Thompson AAR
Thompson C
Thompson M
Thompson R
Thomson EC
Thomson N
Thornton D
Thornton L
Thorpe C
Thrasyvoulou L
Thrush J
Thwaites R
Thwaites RS
Thwaites V
Thwaites V
Tibke C
Tierney C
Tilbey S
Tiller H
Tilney E
Timlick E
Ting L
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Torres Gutiérrez RP
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Torres-Tobar L
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Travers J
Treus E
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Trotman S
Trott S
Trower H
Troya J
Truman N
Trumper E
Tsinaslanidis G
Tucci A
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Tuckey V
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Turki S
Turley C
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Turner P
Turner V
Turner-Bone I
Turney S
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Turtle LCW
Tutt G
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Twiss S
Tyl D
Tyler A
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Valencia-Ramos J
Valido A
van Koutrick L
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Varón B
Vasconcelos RHT
Vassell K
Vedage D
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Velasco-Quirce S
Venkatesh H
Venkatesh H
Verlander M
Vertue M
Verula J
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Villar F
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Villaverde C
Villoslada-Blanco P
Vincent R
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Virseda-Berdices A
Vitart V
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Vuylsteke A
Vélez-Santamaría V
Víctor V
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Walther RA-S
Walton O
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Webster K
Wei S
Weldon CH
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Winmill H
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Winter-Goodwin B
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Wong J
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Woodford C
Woodruff M
Woods L
Woodward E
Woodward J
Woolcock M
Worner R
Worsley L
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Wren L
Wreybrown C
Wright C
Wright DJ
Wright M
Wright S
Wrobel N
Wu Y
Wulandari R
Wylie K
Wynter I
Xavier K
Yang J
Yates B
Ye C
Young M
Yun N
Yáñez Z
Zak A
Zaki A
Zambon M
Zamikula J
Zapatamartinez M
Zapatero-Gaviria A
Zarate R
Zazo S
Zborowski AC
Zechner M
Zechner M
Zhao X
Zheng C
Zitter L
Zongo O
Zorloni C
Álvarez BG
Álvarez-Benítez Y
Álvarez-Navia F
Íñiguez M
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)

Brunel University Research Archive

Whole-genome sequencing reveals host factors underlying critical COVID-19

Author: Abd Elghafar Mohamed S.
Abdel-Aziz Mahmoud
Abdelrazik Marwa
Abdollahi Hamed
Abdullah T.
Abecasis Goncalo
Abedalthagafi M.
Abel Lynn
Abernathy C.
Abraheem Azmeralde
Abul-Husn Noura S.
Acquilini D.
Adams C.
Adams Emma L.
Adams K.
Adamsara Alireza
Adanini Olurenke
Adeleye O.
Adra D.
Afilalo J.
Afilalo M.
Afolabi D.
Afrasiabi Z.
Agasou A.
Agrawal Shruti
Agüero D.
Ahmad N.
Ahmadi Saeideh
Ahmed A.
Ahmed Cecilia
Akeroyd L.
Akhtar M.N.
Akinkugbe O.
Aksentijevich Alexandra
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 Afshar Etemadi
Alexander Peter.
Alfonso J.
Alghamdi B.
Alghamdi J.
Ali A.
Ali Altaf
Ali I.A.M.
Ali Syamlan
Aliannejad Rasoul
Aljawini N.
AlJohani S.
Alkwai S.
Allan A.
Allan E.
Allan J.
Alldis Zoe
Allen L.
Allen Meryem
Allen Schvearn
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 Ali
Amitrano Sara
Anastasescu E.
Anderson F.
Anderson J.
Anderson Madeleine
Anderson Peter
Anderson S.
Anderson S.
Anderson T.
Andolfo I.
Andretta F.
Andreucci E.
Andrew Angela
Andrew B.
Andrew Gratrix
Andrews E.
Andrews Shea J.
Anedda F.
Anemoli V.
Annis A.
Antcliffe David
Antinori Andrea
Antoni M.D.
Anumakonda V.
Apetri E.
Aquino Maia
Arabi Y.M.
Aravindan Latha
Arbane Gill
Archer Katie
Arden T.
Arias Sonia Sousa
Arif S.
Armstrong Jacob
Armstrong Lisa
Armstrong Ruth
Arning N.
Arnold Sophie
Arranz María Jesús
Arribas E.
Artuso R.
Arumugam Prabhu
Ascolillo Steven
Ashraf Saima
Ashton L.
Aslibekyan S.
Astin-Chamberlain Raine
Atkinson E.G.
Attwood B.
Aucella F.
Auld D.
Auld F.
Austin Karen
Austin Pauline
Auton A.
Ayers A.
Azarzar S.
Bachetti T.
Baikady R.R.
Baillie John Kenneth
Baines Balvinder
Baines D.
Baines K.
Baird Yolanda
Bakthavatsalam Dhanalakshmi
Balaconis Mary K.
Baldassarri M.
Ball C.A.
Baltzell A.H.
Bamford A.
Bamford Peter
Banach Dorota
Bancroft Hollie
Band G.
Bandini M.
Bandla Nageswar
Bano S.
Baptista David
Barakeh D.
Baras Aris
Baratti S.
Barber R.
Barberis L.
Barbieri C.
Barclay Lucy
Bargagli E.
Barhoush E.
Barker J.
Barnes K.C.
Baroni S.
Barrett F.
Barron A.
Barry P.
Bartels M.
Bartley Shauna
Baruah R.
Bashyal Archana
Basikolo C.
Bassetti M.
Bastion V.
Bates H.
Bates Michelle
Batini Chiara
Battle Ceri
Bauchmuller K.
Baxter N.
Baya N.
Bayo L.A.
Beadle Jane
Bean S.
Beaumont K.
Beavis S.
Beck A.
Beckmann Noam D.
Bedini J. L.
Bee Catherine E.
Beech E.
Beech Valerie
Beekes M.
Beesley K.
Begg Colin
Beguin Y.
Behan T.
Beith C.M.
Belagodu Zakaula
Belbin Gillian Morven
Belfield H.
Belhaj Y.
Beligni G.
Belisle A.
Bell D.
Bell G.
Bell M.
Bell S.
Bellamy Mary
Belli M.A.
Bellini A.
Bellwood R.
Below Jennifer
Bemand T.
Benetti E.
Benham Leonie
Bennett D.
Bennett Sara
Bentley David
Bentley M.
Benyon S.
Beranova E.
Bercades G.
Bergantini L.
Bergomi P.
Berkowitz Nathan
Bernardo D.
Bevan E.
Bewley J.
Bhatia Nikhil
Bhatterjee Ravi
Bhuie Parminder
Bi R.
Biagio A.D.
Bianchi F.
Bibert S.
Bibi Fatima
Biddle Jack
Biggs Heather
Birch J.
Birch J.
Birch Sophie.
Birchall K.
Birchall K.
Bird S.
Birkinshaw Isobel
Birt M.
Biscarini F.
Black E.
Black K.
Blackledge B.
Blackman H.
Blakemore H.
Blay Natalia
Blow Sara
Blunt M.
Board S.
Bochud P.Y.
Bociek Aneta
Boezen M.
Boillat N.
Bokhari M.
Bolton Matthew
Bolton Rachel
Bonner Stephen
Booker L.
Borislavova B.
Borra Catherine
Botello A.
Botfield Liam
Bottà G.
Bouab M.
Bough L.
Boughton A.P.
Bowes A.
Bowles Ruth
Boyle P.
Boyle R.
Boz Ceilia
Bradford Y.
Bradley C.
Bradley P.
Bradley-Potts Joanne
Bradshaw Zena
Brady A.
Brady M.
Brady R.
Brandwood C.
Branney D.
Brantwood Craig
Brassard N.
Brayne A.
Brealey D.
Bremmer P.
Brenner B.
Bretherick Andrew D.
Brett Michael
Brett Stephen
Brickell K.
Bridgett V.
Brimfield Lutece
Brinkworth Elaine
Briton Kate
Britvan Bari
Bromley M.
Brooke Hollie
Brooks S.
Brown A.
Brown Adam
Brown C.W.
Brown Ellen
Brown Joanna
Bruce M.
Brumpton Ben M.
Bruno Raffaele
Brunton Mark
Bruttini M.
Bryant J.
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Buckley C.
Buckley Sarah
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Burn I.
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Burton Maudrian
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Butcher D.
Butler Aaron
Butler Joanna
Butler S.
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Butterworth A.S.
Butterworth-Cowin N.
Button H.
Buxbaum Joseph D
Cabrelli Louise
Cagova L.
Caldarelli G.P.
Callaghan Marie
Callier S.
Cameli Paolo
Campbell Archie
Campbell Archie
Campbell Helen
Campbell Rachael
Campbell Suzanne
Campos Sara
Camsooksai J.
Canaccini A.
Cantarini L.
Cantor M.N.
Capasso M.
Capitani K.
Cappelli S.
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Carella M.
Carey D.J.
Carmody Margaret
Carmody S.
Carnahan M.
Carreras A.
Carriero M.L.
Carter A.
Carter David
Carter E.
Carter Joseph
Carter S.
Carungcong J.
Casey Matt
Castaño-Vinyals G.
Castelli F.
Castle K.
Castori M.
Caswell Melanie
Catena E.
Caterson Jess
Cathcart Susanne
Catlow L.
Caulfield Mark J.
Cavazza Anna
Cawley Kathryn
Cawthron K.
Ceri S.
Chablani M.
Chadbourn Indra
Chamnanphon Monpat
Chan Georgia
Chan R.
Chandler B.
Chang Xiao
Chapman Susan
Chariyavilaskul Pajaree
Charles B.
Charlesworth Ruth
Charney Alexander W.
Charnock R.
Chasman D.I.
Chassé M.
Chaudhary Kumardeep
Chavan S.
Cheema Yusuf
Chen Hung-Hsin
Chen Jiantao
Cheng N.
Cherian Shiney
Chetam L.
Chetruengchai Wanna
Cheyne C.
Childs D.
Chittoor G.
Cho Judy H.
Cho K.
Choi Sam
Choudhury Yasmin
Christine Almaden-Boyle None
Chukkambotla Srikanth
Churchhouse C.
Chwialkowska Karolina
Claassen S.
Clamp Sarah
Clapham M.
Claringbould A.
Clark Amy
Clark M.
Clark Martynn
Clark Richard
Clark Sarah
Clark Victoria
Clarke D.
Clarke N.
Clarkson M.
Clayton Sarah
Clement Ian
Clements S.
Coates Charlotte
Cockrell Maeve
Coetzee S.
Coghlan Phoebe
Coignet M.
Coiro G.
Coker D.
Cole J.
Cole J.
Cole Stephen
Coleman Dabheoc
Coles Holly
Colley Julie
Collier D.
Collier David
Collins Amy
Collins Brett L.
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Publication venue
Publication date: 01/01/2022
Field of study

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization 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

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