79 research outputs found
Whole-genome sequencing reveals host factors underlying critical COVID-19
- Author
- Abd Elghafar M. S.
- Abdel-Aziz M.
- Abdelrazik M.
- Abdollahi H.
- Abdullah T.
- Abecasis G. R.
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- '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
Erratum: Corrigendum: Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
- Author
- Abril Josep F
- Aerts Jan
- Andersson Leif
- Antonarakis Stylianos E
- Arakawa Hiroshi
- Axelsson Erik
- Backström Niclas
- Bao Zhirong
- Beattie Kevin J
- Bejerano Gill
- Berlin Sofia
- Betran Esther
- Bezzubov Yuri
- Birney Ewan
- Boardman Paul E
- Bonfield James K
- Bork Peer
- Bourque Guillaume
- Brandstrom Mikael
- Brent Michael R
- Brown William R A
- Buerstedde Jean-Marie
- Burt Peer
- Bye Jacqueline M
- Caldwell Randolph B
- Camara Francisco
- Castellano Sergi
- Castelo Robert
- Chatterjee Sourav
- Cheng Ze
- Chiaromonte Francesca
- Chinwalla Asif
- Cliften Paul F
- Clifton Sandra W
- Croning Michael D R
- Crooijmans Richard P M A
- Daniels Laura
- Davies Robert M
- de Jong Pieter J
- Delany Mary E
- Delehaunty Kimberly D
- Dewey Colin
- Dickens Nicholas J
- Dodgson Jerry B
- Dupanloup Isabelle
- Eichler Evan
- Ellegren Hans
- Elnitski Laura
- Emerson J J
- Eswara Pallavi
- Eyras Eduardo
- Fillon Valerie
- Flicek Paul
- Francis Matthew D
- Fronick Catrina
- Fulton Lucinda A.
- Fulton Robert S
- Furey Terrence S
- Goodstadt Leo
- Gordon Laurie
- Grafham Darren V
- Graves Tina A
- Griffin Darren K.
- Griffiths-Jones Sam
- Groenen Martien A M
- Guigo Roderic
- Hardison Ross C
- Harris Robert S
- Harte Rachel A
- Hatzigeorgiou Artemis G
- Haussler David
- He Jianbin
- Hillier LaDeana W
- Hinrichs Angie S
- Hoffman Michael M
- Hubbard Simon J
- Huckle Elizabeth J
- Humphray Sean J
- Inoko Hidetoshi
- International Chicken Genome Sequencing Consortium
- Ivarie Robert
- Jacobbson Lina
- Kaessmann Henrik
- Kaufman Jim
- Kent W James
- Kerje Susanne
- Kierzek Andrzej M
- King David C
- Koriabine Maxim
- Kouranov Andrei
- Kremitzki Colin
- Law Andy S
- Layman Dan
- Letunic Ivica
- Liu Bin
- Long Manyuan
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- Magrini Vincent
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- Mardis Elaine R.
- Masabanda Julio S
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- Nekrutenko Anton
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- Overton Ian M
- Pachter Lior
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- Paterson Andrew H
- Paton Bob
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- Ponting Chris P
- Pourquie Olivier
- Radakrishnan Anusha
- Randall-Maher Jennifer
- Raney Brian
- Reymond Alexandre
- Rijnkels Monique
- Robertson Lindsay
- Rogers Jane
- Romanov Michael N
- Rondelli Catherine M
- Salomonsen Jan
- Scott Carol E
- Searle Stephen M J
- Severin Jessica
- Shiina Takashi
- Shteynberg David D
- Siepel Adam
- Skjoedt Karsten
- Smit Arian F. A.
- Smith Jacqueline
- Smith Scott M
- Speed David
- Stubbs Lisa
- Suyama Mikita
- Taylor James
- Taylor Ruth G
- Tempest Helen G
- Tesler Glenn
- Tickle Cheryll
- Torrents David
- Tuzun Eray
- Tyekucheva Svitlana
- Ucla Catherine
- Ureta-Vidal Abe
- van der Poel Jan J
- Vignal Alain
- von Mering Christian
- Waddington David
- Wallis John W
- Wang Jian
- Wang Jun
- Warren Wesley
- Webber Caleb
- Webster Matthew T
- Wilson Richard K.
- Wilson Stuart A
- Wong Gane Ka-Shu
- Yang Huanming
- Yang Shan
- Yang Shiaw-Pyng
- Yu Jun
- Zdobnov Evgeny M
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 17/02/2005
- Field of study
International Chicken Genome Sequencing Consortium.
The Original Article was published on 09 December 2004.
Nature432, 695–716 (2004).
In Table 5 of this Article, the last four values listed in the ‘Copy number’ column were incorrect. These should be: LTR elements, 30,000; DNA transposons, 20,000; simple repeats, 140,000; and satellites, 4,000. These errors do not affect any of the conclusions in our paper.
Additional information.
The online version of the original article can be found at 10.1038/nature0315
Whole-genome sequencing reveals host factors underlying critical COVID-19
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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
Addressing Safety Issues of Health Care Personnel, Family Members, and the Environment
- Publication venue
- 'American Society of Clinical Oncology (ASCO)'
- Publication date
- Field of study
Primary Care Groups: Developing Organisational Capacity and Relationships
- Author
- Publication venue
- 'Emerald'
- Publication date
- Field of study
Extending the ‘Right of Election’: Men’s Arguments for Women’s Political Representation in Late Enlightenment Britain
- Author
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2005
- Field of study
Natural Rights and the Ninth Amendment: How Does Lockean Legal Theory Assist in Interpretation?
- Author
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2010
- Field of study
Thigh-length compression stockings and DVT after stroke
- Author
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- Publication venue
- 'Elsevier BV'
- Publication date
- 01/07/1994
- Field of study
Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease
'Standing the gaff': Immiseration and its consequences in the de-industrialised mining communities of Cape Breton Island
- Author
- Publication venue
- 'SAGE Publications'
- Publication date
- 05/06/2012
- Field of study
This paper applies Marx’s concept of immiseration to the mining communities of Cape Breton Island, Nova Scotia, in an attempt to conceptualise the consequences of de-industrialisation. We identify and explore a series of specific social, economic, historical, political and geographic circumstances that have militated against the radicalisation predicted by Marx, but nonetheless conclude that the concept of immiseration continues to have contemporary relevance. Economic hardship, out-migration on an unprecedented scale and a collapse of confidence at both an individual and collective level are the consequences of de-industrialisation and reveal the contemporary experience and purpose of immiseration. First, it is a process through which a geographically isolated population of workers have become conditioned either to accept poor work in terms of lower wages and conditions, or to become economic migrants. Second, it is a process through which new opportunities for profitability and investment are established for new investors
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