8 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.
- Abecasis G.R.
- Abedalthagafi M.
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- Abraheem A.
- Abul-Husn N.S.
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- Zucchi P.
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- Zöllner S.
- Åsvold B.O.
- 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
High density operation in dite with neutral beam injection
- Publication venue
- Publication date
- 01/01/1983
- Field of study
SIGLELD:9091.9F(CLM-R--239) / BLDSC - British Library Document Supply CentreGBUnited Kingdo
The geopolitics of laughter and forgetting: A world‐systems interpretation of the post‐modern geopolitical condition1
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- Agnew J.
- Agnew J.
- Appadurai A.
- Arrighi G.
- Arrighi G.
- Balibar E.
- Beck U.
- Beck U.
- Bergesen A.J.
- Block F.
- Brunn S.
- Campbell D.
- Castells M.
- Castells M.
- Colin Flint
- Danielson M.N.
- Derlugian G.M.
- Falk R.
- Fishman R.
- Harvey D.
- Hopkins T.
- Hugill P.J.
- Hugill P.J.
- Klare M.
- Kothari R.
- Köhler G.
- McKenzie E.
- Modelski G.
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- Pelizzon S.
- Sassen S.
- Schwartz H.M.
- Sherman S.
- Smith J.
- Swyngedouw E.
- Taylor P.J.
- Taylor P.J.
- Taylor P.J.
- Wallerstein I.
- Wallerstein I.
- Wallerstein I.
- Wallerstein I.
- Ó Tuathail G.
- Publication venue
- 'Informa UK Limited'
- Publication date
- Field of study
The geography of international trade
- Author
- Publication venue
- 'SAGE Publications'
- Publication date
- 01/09/1994
- Field of study
New classics and diverse clusters in historical geography
- Author
- Publication venue
- 'SAGE Publications'
- Publication date
- Field of study
Company Culture – Its Role in an Industrial Society
- Author
- Abegglen J.C.
- Adams R.M.
- Andow P.
- Andrews K.R.
- Anon
- Barsoux J.L.
- Bartlett S.
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- Berstein A.
- Blake R.R.
- Block B.
- Blocklyn PL.
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- Davis K.
- Davis S.M.
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- De Jonquieres G.
- De Jonquieres G.
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- Dumaine B.
- Editorial
- Eisner A.
- Embrey D.E.
- Engstrom T.W.
- Ernest A. Stallworthy
- Fry J.N.
- Hamermesh R.B.
- Handy C
- Hansen B.L.
- Hansen B.L.
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- Hayes R.
- Heller R.
- Helm L.
- Hornby D.
- Hubbard G.
- Hugill P.J.
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- Jones D.E.
- Joseph J.
- Juran J.M.
- Kantrow A.M.
- Kantrow A.W.
- Kharbanda O.P.
- Kharbanda O.P.
- Koontz H.
- Kosaka M.
- Kreitner R.
- Kubr M.
- Leigh A.
- Lessem R.
- Lorenz C.
- Lorenz C.
- Lowe T.A.
- Manasian D.
- Marous J.
- McCosh A.M.
- McGill M.E.
- Mendonsa E.L.
- Michael S.R.
- Moore T.
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- Moran R.T.
- Moran R.T.
- Moran R.T.
- Moran R.T.
- Naisbitt J.
- Naisbitt J.
- Odiorne G.S.
- Om P. Kharbanda
- Pall G.A.
- Parker C.
- Peel Q.
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- Peters T.J.
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- Price C
- Prokopenko J.
- Radford G.D.
- Rausch D.A.
- Rheingold E.M.
- Robson M.
- Rodger I.
- Rodgers T.J.
- Salazar M.V.
- Sapre S.A.
- Saunders G.
- Schein E.H.
- Seo
- Shetty Y.K.
- Skapinker M.
- Smith G.D.
- Solberg S.L.
- Squires F.H.
- Taguchi G.
- Thackray J.
- Thackray J.
- Thomas M.
- Underwood J.
- Waltem M.
- Waterman J.
- Weick K.G.
- Weiss J.W.
- Whymant R.
- Woods D.D.
- Wuthnow R.
- Yotaro Kobayashi
- Publication venue
- 'Emerald'
- Publication date
- Field of study
Whole-genome sequencing reveals host factors underlying critical COVID-19
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- 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.
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- AlMalik A.
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- Almohammed I.
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- Amirsavadkouhi Ali
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- Andreucci E.
- Andrew Angela
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- Anemoli V.
- Annis A.
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- Apetri E.
- Aquino Maia
- Arabi Y.M.
- Aravindan Latha
- Arbane Gill
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- Armstrong Lisa
- Armstrong Ruth
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- Arnold Sophie
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- Arumugam Prabhu
- Ascolillo Steven
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- Atkinson E.G.
- Attwood B.
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- de Almeida Martins L.G.
- de Cid R.
- de Geus E.
- de Gordoa Laura Ortiz-Ruiz
- de la Cal-Sabater P.
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- Death Y.
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- Dexter Catherine
- Di Angelantonio Emanuele
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- Doddato G.
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- Åsvold Bjørn Olav
- 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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- Sen Gautam
- Shammas Carole
- Sharma Ruchir
- Shaw William H
- Sheridan R.B.
- Sieferle
- Sieferle Rolf Peter
- Sigaut F.
- Simon Julian L
- Skidelsky Robert
- Smil Vaclav
- Smith Adam
- Smith Richard J
- Solow
- Sombart Werner
- Soto
- Sowell Thomas
- Spadafora David
- Spierenburg Pieter
- Spufford Francis
- Stangeland Charles Emil
- Stark Rodney
- Steedman Carolyn
- Steensgaard Niels
- Stein Burton
- Steinfeld Robert J
- Stiglitz Joseph
- Storrs Christopher
- Studwell Joe
- Sun Tu Zen
- Taleb Nassim Nicholas
- Teich Mikulµš
- Teltscher Kate
- Temple Robert
- Thomas Brinley
- Thomas Brinley
- Thomas R.P.
- Tilly Charles
- Tilly Charles
- Toledano E.R.
- Toledano E.R.
- Torres Sµnchez
- Tracy James D
- Tracy James D
- United Nations University International Human Dimensions Programme/United Nations Environment Programme
- Van Dyke Paul A
- Veen
- Verley Patrick
- Vittorio Antonio Di
- Voth Hans-Joachim
- Vries
- Vries
- Vries
- Vries Peer
- Vries Peer
- Vries Woude
- Wade Robert
- Wagenbreth Otfried
- Wakefield D.
- Waley-Cohen Joanna
- Wallerstein Immanuel
- Wallerstein Immanuel
- Wallerstein Immanuel
- Wallerstein Immanuel
- Wallerstein Immanuel
- Wallerstein Immanuel
- Warde Paul
- Warsh David
- Webb Walter Prescott
- Weber Max
- Weber Max
- Weber Max
- Wei Betty
- Weightman Gavin
- Weisser Michael
- White Colin
- Whitehead Alfred North
- Wiles R.C.
- Will Pierre-Étienne
- Williams Eric
- Winch Donald
- Wittfogel Karl August
- Wong Roy Bin
- Woo-Cumings Meredith
- Wood Ellen Meiksins
- Woodman Harold D
- Woodruff William
- Woods Thomas E
- Wright Gavin
- Wright John
- Wright Robert
- Wrigley E.A.
- Wrigley E.A.
- Xiaotong Fei
- Zamagni Vera
- Zanden Jan
- Zanden Jan
- Zanden Jan
- Zelin Madeleine
- Zheng Yangwen
- Zhuang Guotu
- Publication venue
- 'Vandenhoeck & Ruprecht GmbH & Co, KG'
- Publication date
- Field of study