44 research outputs found
Orthodontic tooth movement in the prednisolone-treated rat
- Publication venue
- 'Allen Press'
- Publication date
- 01/04/2000
- Field of study
Adverse effects of corticosteroids on bone metabolism raise concerns as to whether steroid treatment may influence orthodontic movement. This study examined the effect of prednisolone on orthodontic movement using an established rat model. The corticosteroid treated group (N = 6) was administered prednisolone (1 mg/kg) daily, for a 12-day induction period; the control group (N = 6) received equivalent volumes of saline. On day 12, an orthodontic appliance was placed which exerted 30 g of mesial force to the maxillary first molar. Animals were sacrificed on day 24 and tooth movement was measured. Sagittal sections of the molars were stained with haematoxylin and eosin, and for tartrate-resistant acid phosphatase (TRAP) activity. While there were no significant differences in the magnitude of tooth movement between the 2 groups, steroid-treated rats displayed significantly less root resorption on the compression side and fewer TRAP-positive cells within the PDL space on the same side. This suggests steroid treatment suppressed elastic activity
Whole-genome sequencing reveals host factors underlying critical COVID-19
- Author
- Abd Elghafar M. S.
- Abdel-Aziz M.
- Abdelrazik M.
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- Veerapen K.
- Venkatesh H.
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- Wackett T.
- Wadams B.
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- Wagstaff V.
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- Wanying Z.
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- Ward M.
- Warden S.
- Warmerdam R.
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- Weaver J.
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- Weston H.
- Whileman A.
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- White K.
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- Whiteley S.
- Whiteside J.
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- Wilkinson B.
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- Williams E.
- Williams F.
- Williams G.
- Williams H.
- Williams K.
- Williams M.
- Williams P.
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- Willis H.
- Wills M.
- Willson J.
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- Wilson D. J.
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- Wilson J. F.
- Winnard S.
- Winter-Goodwin B.
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- Wolford B.
- Wong J.
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- Wood H. -L.
- Wood S.
- Wood T.
- Woodford C.
- Woodruff M.
- Woods L.
- Woodyatt W.
- Woolley A. E.
- Worner R.
- Worsley L.
- Wray G.
- Wren L.
- Wright D.
- Wright J.
- Wright M.
- Wrobel N.
- Wu Y.
- Wulandari R.
- Wyllie D. H.
- Wynter I.
- Xavier K.
- Xue X.
- Yadav A.
- Yang J.
- Yassen A. M.
- Yates B.
- Ye C.
- Yun N.
- Zainy T.
- Zak A.
- Zaki A.
- Zamikula J.
- Zanella I.
- Zborowski A. C.
- Zeberg H.
- Zechner M.
- Zguro K.
- Zhang M.
- Zhao J. H.
- Zheng C.
- Zhou W.
- Zitter L.
- Zlatopolsky M.
- Zollner S.
- Zongo O.
- Zucchi P.
- Zyndorf M.
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2022
- Field of study
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
Genetic mechanisms of critical illness in COVID-19.
- Author
- A A Roger Thompson
- A Abraheem
- A Agasou
- A Ahmed
- A Ali
- A Allan
- A Altabaibeh
- A Alvaro
- A Aspinwall
- A Ayers
- A Bamford
- A Barron
- A Bashyal
- A Bellini
- A Bociek
- A Botello
- A Bowes
- A Brady
- A Brayne
- A Brown
- A Brown
- A Butler
- A Campbell
- A Carter
- A Collins
- A Cowley
- A Cowton
- A Cowton
- A Cox
- A Crew
- A Dance
- A Daniel
- A Daniels
- A Dela Rosa
- A Drummond
- A Durie
- A E Heron
- A Easthope
- A Easthope
- A Evans
- A Fofano
- A Gales
- A Ganesan
- A Gardner
- A Garg
- A Gherman
- A Gordon
- A Gratrix
- A Gulati
- A Gupta
- A Haigh
- A Haldeos
- A Harrison
- A Harvey
- A Hayes
- A Higham
- A Higham
- A Hilldrith
- A Holden
- A Hormis
- A Hutcheon
- A Javaid
- A Joseph
- A Kaliappan
- A Katary
- A Kay
- A Kayani
- A Kent
- A Kirkby
- A Knight
- A Kubisz-Pudelko
- A Kuravi
- A Lewis
- A Loveridge
- A Lyle
- A Mayer
- A McAlpine
- A McCarthy
- A McGregor
- A McGregor
- A Meikle
- A Mitchell
- A Mitra
- A Morris
- A Morrison
- A Naranjo
- A Nicholson
- A Nicholson
- A Nilsson
- A Noakes
- A Patel
- A Pickard
- A Poole
- A Price
- A Puxty
- A Quinn
- A Quinn
- A Raithatha
- A Rattray
- A Reddy
- A Reed
- A Reyes
- A Rose
- A Rose
- A Rostron
- A Roy
- A Roynon-Reed
- A S Raj
- A Salberg
- A Sanderson
- A Serrano-Ruiz
- A Solesbury
- A Sukha
- A Swain
- A Tariq
- A Thomas
- A Thomas
- A Todd
- A Tomas
- A Tridente
- A Tucci
- A Turnbull
- A Uriel
- A Ustianowski
- A Vochin
- A Vuylsteke
- A Waite
- A Walden
- A Whileman
- A Wilkinson
- A Williams
- A Williams
- A Wilson
- A Zak
- A Zaki
- Achille Iolascon
- Adam Auton
- Adam Brown
- Agnese Verzuri
- Agostino Ognibene
- Agostino Riva
- Ailsa Golightly
- Alan Maclean
- Alessandra
- Alessandra Stella
- Alessandra Vergori
- Alessia Giorli
- Alexander J Mentzer
- Alice Donati
- Alison M Meynert
- Alistair Nichol
- Ana da Silva Filipe
- Andrea Antinori
- Andrea Cossarizza
- Andrea Ganna
- Andrea Tommasi
- Andrew Rambaut
- Andrew Stenhouse
- Andy Law
- Anjali J Shastri
- Anna Canaccini
- Anna Maria Pinto
- Annarita Giliberti
- Annemarie B Docherty
- Antonella D'Arminio Monforte
- Antonia Ying Wai Ho
- Antonio Di Biagio
- Antony Symons
- Arianna Emiliozzi
- Arianna Gabrieli
- Audrey Coutts
- B Anwar
- B Attwood
- B Baines
- B Blackledge
- B Borislavova
- B Chandler
- B Charles
- B Creagh-Brown
- B David
- B Deacon
- B Deacon
- B Digby
- B Faulkner
- B Fuller
- B Gumbrill
- B Gurung
- B Hadebe
- B Hairsine
- B Hopkins
- B Johnston
- B Lenagh
- B Masunda
- B Ogg
- B Patel
- B Player
- B Purewal
- B Scholefield
- B Shelley
- B Sloan
- B Thomas
- B Wadams
- B Welsh
- B Wilkinson
- B Winter-Goodwin
- B Yates
- Baillie J Kenneth
- Barbara Rossetti
- Beale Rupert
- Beatrice Alex
- Benjamin Bach
- Bretherick Andrew D
- Bruno Frediani
- C Adams
- C Ahmed
- C Almaden-Boyle
- C Ashbrook-Raby
- C Basikolo
- C Battle
- C Beazley
- C Beith
- C Borra
- C Brandwood
- C Brantwood
- C Burnett
- C Castro Delgado
- C Clark
- C Clulow
- C Collins
- C Cruz
- C Davis
- C Demetriou
- C Dennis
- C Dexter
- C Downes
- C Dunmore
- C Eastgate
- C Eckbad
- C Finch
- C Gibson
- C Gorman
- C Hays
- C Hewitt
- C Holl
- C Howcroft
- C Humphrey
- C Jackson
- C Jardine
- C Jennings
- C Jones
- C Kaye
- C Lynch
- C Lyons
- C McCulloch
- C McParland
- C McParland
- C Murphy
- C Parmar
- C Pawley
- C Phillips
- C Phillips
- C Pothecary
- C Pothecary
- C Prendergast
- C Price
- C Rishton
- C Sell
- C Shovelton
- C Sicat
- C Stuart
- C Summers
- C Swan
- C Thompson
- C Thorpe
- C Tibke
- C Tierney
- C Vigurs
- C Wells
- C Whitton
- C Whyte
- C Wrey Brown
- Cameron J Fairfield
- Carmelo Piscopo
- Carmen Marciano
- Caroline Abernathy
- Carrol Gamble
- Caterina Lo Rizzo
- Catherine A Shaw
- Catherine H Weldon
- Caulfield Mark
- Ceilia Boz
- Cesira Nencioni
- Chelsea Ye
- Chiara Fallerini
- Chiara Gabbi
- Chiara Spertilli
- Chloe Donohue
- Chris Ponting
- Christoper A Green
- Cinthia E Jannes
- Clare Jackson
- Clohisey Sara
- Cristina Mussini
- D Antcliffe
- D Bakthavatsalam
- D Banach
- D Baptista
- D Bell
- D Branney
- D Brealey
- D Brealey
- D Butcher
- D Butcher
- D Childs
- D Clarke
- D Collier
- D Collier
- D Cristiano
- D Dawson
- D Donaldson
- D Duffin
- D Fottrell-Gould
- D Golden
- D Griffin
- D Hamilton
- D Hawcutt
- D Hope
- D Horner
- D Kallon
- D Kaye
- D Kelly
- D Loader
- D Lomas
- D Martin
- D McGlynn
- D McLaughlanv
- D Melia
- D Menzies
- D Mullan
- D Pogson
- D Potla
- D Potoczna
- D Purohit
- D Raynard
- D Salutous
- D Salutous
- D Scaletta
- D Shaw
- D Skinner
- D Smyth
- D Strachan
- D Tetla
- D Thornton
- D Trodd
- D Vedage
- D Walker
- D Warren
- D Williams
- D Wood
- D Wright
- Daniela Francisci
- Daniella Coker
- Danilo Tacconi
- David A van Heel
- David Bennet
- David L Robertson
- David Stuart
- Dawn Law
- Debby Bogaert
- Derek Murphy
- Domenico A Coviello
- E Abaleke
- E Allan
- E Anastasescu
- E Andrews
- E Apetri
- E B Jude
- E Beech
- E Beranova
- E Bevan
- E Black
- E Brinkworth
- E Collins
- E Combes
- E Davies
- E Dobson
- E Dooks
- E Fisher
- E Gendall
- E Goff
- E Goodwin
- E Gordon
- E Heeney
- E Horsley
- E Hughes
- E Johnson
- E Knights
- E Lee
- E London
- E Maccacari
- E Massey
- E McKenna
- E Meadows
- E Moncur
- E Morino
- E Mwaura
- E Peasgood
- E Perkins
- E Radford
- E Raith
- E Raith
- E Salciute
- E Smith
- E Smithson
- E Stoddard
- E Stones
- E Thomas
- E Tilney
- E Timlick
- E Treus Gude
- E Virgilio
- E Watson
- E Wilby
- Edoardo Conticini
- Egle Saviciute
- Elena Bargagli
- Elena Desanctis
- Elisa Benetti
- Elisa Frullanti
- Elisabetta Menatti
- Elisabetta Schiaroli
- Ellie Mcmaster
- Emma C Thomson
- Emmanuelle Marques
- Enrico Martinelli
- Esther Duncan
- Esther Merlini
- Ewen M Harrison
- F Anderson
- F Auld
- F Bibi
- F Davies
- F Farquhar
- F Fisher
- F Hurford
- F Kibutu
- F McNeela
- F Moore
- F Nasir
- F Trim
- F Wakinshaw
- F Williams
- Fabio Lena
- Fawkes Angie
- Federico Anedda
- Federico Franchi
- Ferdinando Giannattasio
- Filip Taneski
- Filippo Aucella
- Filippo Biscarini
- Floriana Valentino
- Fourman Max Head
- Francesca Andretta
- Francesca Fava
- Francesca Gatti
- Francesca Mari
- Francesca Montagnani
- Francesco Castelli
- Francesco Raimondi
- Furniss James
- G Andrew
- G Arbane
- G Bell
- G Bercades
- G Croston
- G Debreceni
- G Durrant
- G Hambrook
- G Hobden
- G Houston
- G Hughes
- G Jones
- G Lubimbi
- G Maloney
- G Martir
- G Millen
- G Mills
- G O'Connor
- G Padden
- G Randell
- G Sadera
- G Seddon
- G Sera Howe
- G Sloane
- G Subramanian
- G Tsinaslanidis
- G Turner
- G Watson
- G Wray
- Gabriella Coiro
- Gabriella Doddato
- Gail Carson
- Gardar Sveinbjornsson
- Gary Leeming
- Genni Spargi
- Georgios Pollakis
- Giacomo Zanelli
- Gian Piero Caldarelli
- Giancarlo Bosio
- Giuseppe Fiorentino
- Giuseppe Merla
- Gountouna Elvina
- Graham S Cooke
- Griffiths Fiona
- Grimes Graeme
- H Bancroft
- H Bates
- H Belfield
- H Blackman
- H Blakemore
- H Brooke
- H Button
- H Coles
- H Curgenven
- H Filipe
- H Fox
- H Golding
- H Hill
- H Holcombe
- H Houlden
- H Jeffrey
- H Kent
- H Langton
- H McGuinness
- H Meghari
- H Millward
- H Moore
- H Parker
- H Pearson
- H Prady
- H Quinn
- H Rangarajan
- H Rehman
- H Reschreiter
- H Riley
- H Sainsbury
- H Savill
- H Sturgeon
- H T-Michael
- H Tench
- H Tiveran
- H Turner
- H Whittle
- H Willis
- H Wood
- Haley Chris
- Hanning Mal
- Harrison David
- Hayley Hardwick
- Hayward Caroline
- Helen Szoor-McElhinney
- Hinds Charles
- Ho Antonia
- Horby Peter
- I Ali Mohamed Ali
- I Balagosa
- I Birkinshaw
- I Burn
- I Chadbourn
- I D Clement
- I Edmond
- I Frost
- I Hass
- I Hussain
- I Lancoma-Malcolm
- I Leadbitter
- I Nagra
- I Otahal
- I Otahal
- I Turner-Bone
- I Welters
- I White
- I Wynter
- Ilaria Meloni
- Immacolata Andolfo
- Isabella Zanella
- J Allan
- J Barker
- J Bewley
- J Biddle
- J Birch
- J Birch
- J Bradley-Potts
- J Brown
- J Bryant
- J Butler
- J Camsooksai
- J Carter
- J Caterson
- J Cebrian Suarez
- J Cockerill-Taylor
- J Cole
- J Colley
- J Cooper
- J Cupitt
- J Cuttler
- J Daglish
- J Dasgin
- J Dawson
- J Dearden
- J Deery
- J Donnachie
- J Dykes
- J Easton
- J Egan
- J Fernandez Roman
- J Finn
- J Fletcher
- J Frankham
- J Gaylard
- J Gill
- J Godden
- J Goodsell
- J Gregory
- J Greig
- J Gurasashvili
- J Hardy
- J Harris
- J Hatton
- J Hawes
- J Highgate
- J Hornsby
- J Hulme
- J Hunt
- J Hutter
- J Ingham
- J Jones
- J Jones
- J K Baillie
- J Kassam
- J Kenneth Baillie
- J Kenneth Baillie
- J Keshet-Price
- J Liew
- J Little
- J Mallinson
- J Martin
- J Matthews
- J McCormick
- J Medhora
- J Melville
- J Moreno Cuesta
- J Morgan
- J Naisbitt
- J Norris
- J North
- J Parkin
- J Pendlebury
- J Perez
- J Perry
- J Pheby
- J Philbin
- J Pinnell
- J Queiroz
- J Radhakrishnan
- J Reid
- J Rhodes
- J Riches
- J Ritzema
- J Ruddy
- J Ryan-Smith
- J Scriven
- J Scriven
- J Scriven
- J Shiel
- J Singh
- J Singleton
- J Smith
- J Sowter
- J Strickley
- J Summers
- J Taylor
- J Tebbutt
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- J Thrush
- J Tomlinson
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- J Wilkins
- J Willson
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- Janet Harrison
- Janet T Scott
- Janie F Shelton
- Jen Meikle
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- Johnny Millar
- Jorge Esparza-Gordillo
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- K Hanson
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- K Holdroyd
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- K Hugill
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- K King
- K Knowles
- K Lang
- K Liyanage
- K Manso
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- K Postlethwaite
- K Potts
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- K Praman
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- K Pritchard
- K Puxty
- K Reid
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- K Rooney
- K Sellick
- K Shuker
- K Simpson
- K Simpson
- K Slevin
- K Smith
- K Sollesta
- K Stammers
- K Stroud
- K Sweet
- K Tatham
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- K Webster
- K White
- K Williams
- K Xavier
- Katarzyna Hafezi
- Keating Sean
- Kenneth A Mclean
- Kirstie Morrice
- Klaric Lucija
- Klenerman Paul
- Knight Julian
- Kousathanas Athanasios
- L Abel
- L Akeroyd
- L Allen
- L Armstrong
- L Barclay
- L Benham
- L Botfield
- L Bough
- L Brimfield
- L Bunni
- L Cabrelli
- L Cagova
- L Catlow
- L Ding
- L Ferguson
- L Folkes
- L Foster
- L Garner
- L Gemmell
- L George
- L Glass
- L Glass
- L Gledhill
- L Grauslyte
- L Grimmer
- L Gurr
- L Harrison
- L Hodgson
- L Hudig
- L Keating
- L Kittridge
- L Lankester
- L Lennon
- L Lim
- L Ma
- L Marshall
- L Matupe
- L McMorrow
- L McQuillan
- L Mew
- L Mostoles
- L Mwaura
- L Newey
- L O'Brien
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- L O'Neill
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- L Ortiz-Ruiz de Gordoa
- L Park
- L Pippard
- L Prentice
- L Rad
- L Ramos
- L Riddles
- L Roche
- L Roche
- L Rooney
- L Rosaroso
- L Shaw
- L Smith
- L Stevenson
- L Symon
- L Thomis
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- L Thrasyvoulou
- L Ting
- L Tonks
- L Turner
- L van Koutrik
- L Wilcox
- L Wild
- L Wilding
- L Woods
- L Wren
- L Zitter
- Lance C W Turtle
- Laura Bergantini
- Laura Di Sarno
- Laura Marsh
- Laura Merson
- Law Andrew
- Leonardo Croci
- Lia Crotti
- Ling Lowell
- Lisa Norman
- Lorenzo Salerni
- Lorna Donnelly
- Louise Cullum
- Louise Macgillivray
- Louise Sigfrid
- Luca Cantarini
- Luca Guidelli
- Luca Masucci
- Luisa Tavecchia
- M Abdelrazik
- M Al-Moasseb
- M Balasubramaniam
- M Bates
- M Bellamy
- M Birt
- M Blunt
- M Bokhari
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- M Breekes
- M Brett
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- M Carmody
- M Carnahan
- M Casey
- M Caswell
- M Chablani
- M Clapham
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- M Clark
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- M Croft
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- M Patel
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- M Peters
- M Popescu
- M Poulaka
- M Purewal
- M Raj
- M Robinson
- M Sangombe
- M Shankar-Hari
- M Sim
- M Slaughter
- M Smith
- M Smith
- M Spivey
- M T Hijazi
- M Taylor
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- M Thankachen
- M Thirumaran
- M Thomas
- M Tolson
- M Usher
- M Varghese
- M Verlander
- M Vertue
- M Watters
- M White
- M Wiles
- M Williams
- M Wills
- M Woodruff
- M Young
- Maaike Swets
- Mahdad Noursadeghi
- Manu Shankar-Hari
- Marco Castori
- Marco Feri
- Marco Gori
- Marco MandalÃ
- Marco Sita
- Margherita Baldassarri
- Mari E K Niemi
- Mari Ward
- Maria Antonietta Mazzei
- Maria Antonietta Mencarelli
- Maria Bandini
- Maria Eugenia Quiros-Roldan
- Maria Palmieri
- Maria Zambon
- Marie Connor
- Mario Capasso
- Mario U Mondelli
- Marta Corridi
- Maslove David
- Massimiliano Fabbiani
- Massimo Carella
- Massimo Girardis
- Massimo Palmarini
- Massimo Vaghi
- Matteo Bassetti
- Matteo Della Monica
- Matteo Siano
- Mattia Cordioli
- Maurizio Sanarico
- Maurizio Sanguinetti
- Maurizio Spagnesi
- McAuley Danny
- Meera Chand
- Meynert Alison
- Michelle Girvan
- Millar Jonathan
- Mirella Bruttini
- Miriana D'Alessandro
- Montgomery Hugh
- Moore Shona C
- Moutsianas Loukas
- Murphy Lee
- Murray Wham
- N Ahmad
- N Bandla
- N Baxter
- N Boyle
- N Capps
- N Clarke
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- Nichol Alistair
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- O Adanini
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- Oosthuyzen Wilna
- Openshaw Peter J M
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- Paul Klenerman
- Pereira Alexandre C
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- Pier Giorgio Scotton
- Pierpaolo Parravicini
- Pietro Pinoli
- Ponting Chris P
- Porteous David J
- R Astin-Chamberlain
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- Russell Clark D
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- Ruth Lyons
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- S Srikaran
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- S Swann
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- S Turney
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- S Wood
- S Yussuf
- Sabino Scolletta
- Samreen Ijaz
- Sandro Mancarella
- Sandro Panese
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- Sergio Daga
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- Shen Xia
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- Sophie Venturelli
- Stefania Mantovani
- Stefano Baratti
- Stefano Ceri
- Stefano Rusconi
- Stella Aslibekyan
- Stephanie Roberts
- Stephen R Knight
- Summers Charlotte
- Susanna Croci
- Susanna Guerrini
- T Anderson
- T Arden
- T Baird
- T Behan
- T Bemand
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- T Coventry
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- T Joefield
- T Kannan
- T Lawton
- T Marsden
- T Martin
- T McHugh
- T Newman
- T Nortcliffe
- T O Jones
- T Pogreban
- T Rees
- T Samakomva
- T Smith
- T Smith
- T Szakmany
- T Varghes
- T Williams
- T Wood
- Tammy Gilchrist
- Tenesa Albert
- Teresa Filshtein-Sonmez
- Thomas M Drake
- Thushan de Silva
- Tim Walsh
- Tom Fletcher
- Tom Solomon
- Tony Wackett
- Trevor Paterson
- Tullio Trotta
- Turtle Lance
- U Poultney
- V Amin
- V Anumakonda
- V Bastion
- V Cannons
- V Crickmore
- V Gopal
- V Irvine
- V Kasipandian
- V Krishnamurthy
- V Lake
- V Linnett
- V Martinson
- V Nagarajan
- V Page
- V Parris
- V Parris
- V Pristopan
- V Ratnam
- V Rivers
- V Sarathy
- V Thomas
- V Thwaites
- V Tuckey
- V Turner
- V Wagstaff
- V Waugh
- Valentina Anemoli
- Vanessa Sancho-Shimizu
- Victoria Shaw
- Vitart Veronique
- W Harrison
- W Khaliq
- W Khaliq
- W McCormick
- W Woodyatt
- Walker Susan
- Walsh Timothy
- Wang Bo
- Wei Shen Lim
- Wendy S Barclay
- William A Paxton
- William Greenhalf
- Wilson James F
- Wrobel Nicola
- Wu Yang
- X Qiu
- Y Baird
- Y Choudhury
- Y Hussain
- Y Jackson
- Y Thirlwall
- Yang Jian
- Yang Zhijian
- Z Alldis
- Z Belagodu
- Z Bradshaw
- Z Coton
- Z Daly
- Z Farzad
- Z Fernandez
- Z Garland
- Z Maqsood
- Z Omar
- Z Prime
- Z Scott
- Zechner Marie
- Zhai Ranran
- Zheng Chenqing
- Publication venue
- Nature
- Publication date
- 01/01/2020
- Field of study
Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice
Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans
- Author
- Abbasi Z
- Abdul-Hamid M Akhlil
- Abel Paul D
- Abrams Paul H
- Adab Fawzi A
- Adamson Andrew
- Adeyoju A
- Adolfson Jan
- Afzal Naveed
- Ahiaku Ernest K N
- Ahmed Munir
- Al Sudani Mohammed L
- Al-Samarraie Amir S M
- Al-Samerraie [Unknown]
- Al-Singary Waleed
- Al-Sudani [Unknown]
- Alcock Christopher
- Alexander Kimberly
- Ali Zulfiqar
- Almond David J
- Alonzi Roberto
- Aly Markus
- Amin Al Olama Ali
- Anderson John
- Andrews Henry
- Andrews Steven
- Anjum Iqbal
- Anson Ken
- Anyamene Nicola A
- Apakama Ike
- Aparcia F
- Archbold J A A
- Arndt Volker
- Ash D
- Ashford Richard F U
- Auvinen Anssi
- Azzabi A
- Badenoch David
- Bahl Amit
- Bailey Karen
- Bailey M J
- Ball Andrew J
- Banerjee G
- Barber Jim
- Barber N
- Baria [Unknown]
- Barnes Douglas G
- Barros-Silva Joao
- Barwell Julian
- Bashir J
- Basu Pradip
- Bates Christopher A
- Batra Jyotsna
- Bax N A
- Baxter-Smith D
- Bdesha Amar
- Beacock Christopher J M
- Beaney Ronald P
- Beard Ralph
- Beatty John D
- Beck Rupert
- Beese Gail
- Beesley Sharon
- Bell C Richard W
- Bellringer James
- Benlloch Garcia Sara
- Benson Richard
- Beresford [Unknown]
- Bevis Christopher R A
- Bhana Rajanee
- Bhanot S
- Bhatnagar A
- Bhatt R I
- Birch Brian
- Birtle Alison
- Bishop M
- Biyani C Shekhar
- Blacklock A R E
- Blades Rosemary
- Bliss Peter
- Bloomfield David J
- Boddy S
- Bollina Prasad
- Bonnington Sue
- Booth C M
- Bose Pradeep
- Bott Michael C
- Bottomley David
- Boucher Nigel R
- Bowen J
- Bower Mark
- Bowsher W G
- Boyd P J R
- Bradshaw Lynne
- Bramble F James
- Brenner Hermann
- Brewster Simon F
- Briggs Tim
- Brock Cathryn
- Brock Sue
- Bromage Stephen
- Broms Michael
- Brough Richard
- Brown Andrew A
- Brown Paul
- Brown Paul M
- Brown Richard
- Brown Stephen
- Browning Tony J
- Bryan N
- Burgess Neil A
- Burns-Cox Nicholas
- Butterbach Katja
- Butterworth Paul C
- Cahill D
- Callaghan P S
- Calleary John
- Calleja M
- Calman Frances
- Camilleri Philip
- Campbell Alister
- Cannon Andrea
- Cannon-Albright Lisa
- Carnell Dawn M
- Carr T W
- Carter Adam C
- Carter Charles J M
- Carter Simon
- Castle Bruce M
- Catto James
- Cavalli-Bjoerkman Carin
- Chadwick David
- Chahal Rohit
- Chakraborti P
- Chappell [Unknown]
- Charig C
- Chetiyawardana Anula D
- Chilton Christopher
- Chinegwundoh F I
- Chong Irene
- Choudhury Ananya
- Chow Wai-Man
- Christmas Timothy J
- Christova Svetlana
- Churn Mark J
- Cieza-Borrella Clara
- Clarke Noel W
- Clavijo-Eisele Jorge
- Clements Judith A
- Coe M
- Coetzee Gerhard A
- Cohen N P
- Coker C
- Cole David J
- Cole O
- Cole Trevor
- Collins Angus
- Collins Gerald
- Collinson Matthew
- Conn I
- Connell C
- Conti David V
- Cook Audrey
- Cook Margaret
- Cooke Peter
- Cooksey Graeme
- Coombs L
- Cooper Debbie
- Copland Robert F
- Cornaby Andrew J
- Cornford P A
- Corolis [Unknown]
- Corr John
- Costello C B
- Coull Mrs N
- Cowan Richard
- Cox Angela
- Cox Robert
- Coyle C
- Crew Jeremy
- Crisp John C
- Cross W
- Cruger Dorthe
- Crundwell Malcolm
- Cummings [Unknown]
- Cybulski Cezary
- Dadaev Tokhir
- Dahar Nazeer
- Daniel Francis N
- Darrad J
- Daruwala Pallon
- Das Gautam
- Datta Shibendra
- Davidson S
- Davies Joseph
- Davis Michael
- Davison Owen W
- Dawkins Guy
- Dawson Chris
- De Bolla Alan R
- Dearnaley David
- Desai Ken M
- Deutsch George P
- Dick John
- Dickinson Andrew J
- Dickson Jeanette
- Dikov Tihomir
- Dinneen Michael
- Dixit Sanjay
- Dobbs H Jane
- Doble A
- Doble Andrew
- Dodds David
- Doherty Alan
- Donaldson P
- Donovan Jenny L
- Dooldeniya M
- Douglas S Fiona
- Down Liz
- Drake [Unknown]
- Duchesne Gill M
- Duffy Peter
- Dunn Michael
- Dunsmuir W D
- Durkan Garrett
- Durrani Sajid K
- Easton Douglas
- Eaton Alan C
- Eccles Diane
- Eckert Allison
- Eddy B
- Eden C D
- Edwards J
- Eeles Rosalind A
- El-Modir A
- Elkabir Jeremy
- Elliott Emma
- Elliott P Tony
- Ellis B W
- Ellis R
- Elves Andrew W S
- Elwell Christine
- Emberton Mark
- Emmerson Louise
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- Errington R D
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- Fawcett Derek
- Featherston C
- Featherstone Carolyn J
- Feggetter Jeremy
- Ferguson C
- Fermont D
- Ferro Michael
- Fisher Cyril
- Fitzgerald Liesel
- Fitzgerlad Liesel M
- Fletcher Matthew
- Folkes A
- Ford Trevor F
- Foster Paul W
- Franks Kevin N
- Freedman Mathew
- Frim Olivera
- Gale Joanna
- Gallegos Christopher
- Gelister James S
- George Anne
- Ghana [Unknown]
- Gibbs Stephanie
- Gilbert Hugh
- Giles Graham G
- Gillatt David
- Glaholm John
- Glass Jonathan M
- Glenister James
- Goode Thomas D
- Gordon E M
- Govindasami Koveela
- Gower Richard L
- Graham John
- Green Damian
- Greenland Jonathan
- Grieve Robert
- Griffiths Thomas R L
- Gronberg Henrik
- Gujral Sandy
- Gupta Nishi
- Gurun Riza Murat
- Gustafsson Sven
- Guy Michelle
- Guy Peter J
- Haiman Christopher A
- Haldar Neil
- Halder N
- Haley James
- Hamdy F C
- Hamdy Freddie
- Hamilton C
- Hammonds John
- Hampson S J
- Hanbury Damien C
- Hardman P D John
- Harland Stephen J
- Harney John M
- Harper Peter
- Harris D
- Harris Sarah
- Harrison G S M
- Harriss D R
- Harvey-Hills N
- Hawkyard Simon
- Hazel Steve
- Hazelett Dennis J
- Heath Catherine M
- Heathcote Peter
- Hehir Michael
- Hellawell Giles O
- Henderson Brian E
- Hendry David
- Henley Mike
- Henrique Rui
- Henry Ann
- Herbert Pippa
- Herkommer Kathleen
- Hetherington John
- Hickish Tamas
- Hicks James A
- Hilman Serena
- Hindley Richard
- Hindmarsh John R
- Hines John
- Hingorani M
- Ho Edwin T S
- Hodgson Shirley
- Hoffman U
- Holden David
- Holding Peter
- Hollingdale A
- Hollins Graham W
- Holmes Simon A V
- Holt Sarah
- Hopper John L
- Horan Gail
- Horwich Alan
- Hoskin Peter
- Howell Graham P
- Howson Joanne
- Hrouda D
- Huddart Robert
- Hudson Liz
- Hughes Michael
- Hughes Owen
- Hughes Rob
- Humber Caroline
- Iacovou John W
- Ibrahim A
- Inglis John A
- Irving Stuart
- Irwin C
- Iversen Peter
- Izatt Louise
- Izegbu Victor
- Jameel Basharat
- James Michael J
- James N
- James R Lester
- Javle Pradip
- Jenkins P
- Jhavar Sameer
- Johansson Jan-Erik
- Jones Chris R
- Jones David A
- Jones Gareth
- Jones Mandy
- Joseph J
- Joss Shelagh
- Jugurnauth-Little Sara
- Kachakova Darina
- Kaisary Amir
- Kaliski Alexandre L
- Kaneva Radka
- Kapur G
- Karim O
- Karlsson Ami
- Karp Stephen J
- Kedda Mary-Anne
- Keeley F X
- Kelkar Anand R
- Kelleher J P
- Kelly John
- Kenwrick Sue
- Kerr Kris
- Key Tim J
- Khan F
- Khaw Kay-Tee
- Khoo Vincent
- Kibel Adam S
- Kierzek Andrzej
- Kimber Rachel M
- Kinder R
- Kirby Roger S
- Kirk David
- Kirkbride Peter
- Kirollos Magdi M
- Klarskov Peter
- Kluzniak Wojciech
- Kockelbergh Roger
- Koenig Philip C W C
- Kooiman Gordon G
- Koreich O
- Kote-Jarai Zsofia
- Koupparis Anthony
- Kourah Mohamed
- Kraus Sigurd
- Kujala Paula
- Kujawa Magda L
- Kulkarni Ravi
- Kumar M
- Kumar Rajeev
- Kunkler Ian H
- Kynaston H
- Kynaston Howard
- Lachlan Katherine L
- Laing Robert
- Lalloo Fiona
- Lancashire M
- Lane Athene
- Langley Stephen E M
- Laniado Marc
- Larner T R
- Lau Maurice W
- Lawrence W T
- Lawson Anne
- Le Roux Pieter J
- Leader Mary
- Lee A
- Lee J O
- Lee L
- Lemburger R John
- Lennon Teresa
- Leone Priscilla
- Leongamornlert Daniel
- Lester Jason
- Leung Hing
- Lewis D Christopher
- Lewis J
- Li Qiuyan
- Lim Hui-Yi
- Lin Hui-Yi
- Liston Thomas
- Livni Naomi
- Livsey Jacqueline
- Lloyd S
- Locke Imogen
- Lodge Richard
- Logue John
- Longmuir Mark
- Lophatananon Artitaya
- Lophatonanon Artitaya
- Lubinski Jan
- Lucas Malcolm G
- Luedeke Manuel
- Luscombe C J
- Lydon Anna
- Lynch Michael
- Lynn Naing N K
- Lyons Norma
- MacDermott James P A
- Macdonagh Ruaraidh P
- Macdonald [Unknown]
- Madaan Sanjeev
- Madhava Kudingila R
- Maeaettaenen Liisa
- Maguire Joseph
- Maher E R
- Mahmood Rana
- Maia Sofia
- Maier Christiane
- Mair Graeme H M
- Malone Greg
- Malone Peter R
- Mangar Stephen A
- Mantle Mark
- Mark I
- Marsden Gemma
- Mason M D
- Mason Malcolm
- Mason Robert
- Matanhelia [Unknown]
- Matenhelia Shyam
- Matthews Philip N
- McAleese J
- McBride Donna
- Mcdonnell Shannon K
- McDonnell Shannon K
- McFarlane Jonathan
- McGrath [Unknown]
- McIlhenny Craig
- McInerney Paul
- McIntosh Gregor
- McKinna F
- McLaren Duncan
- McLarty Esther
- McMenemin Rhona
- McNeill Alan
- McNicholas T A
- Meddings Robert N
- Mee A David
- Melcher Lucinda
- Memon [Unknown]
- Menzes Pravin
- Michael Agnieszka
- Miller Marek
- Mills Robert
- Mitchell S
- Mitev Vanio
- Mithal Natasha
- Mitkova Atanaska
- Mitra Anita
- Mobb Gillian E
- Moffat Leslie E F
- Mokete [Unknown]
- Money-Kyrle Julian
- Montgomery Bruce
- Moody Hilary
- Moody Martin P
- Morgan Angela
- Morley Roland
- Morris Sean B
- Morrison Patrick
- Mort Diana
- Mostafid Amir H
- Motiwala Hanif
- Mufti Gulzar
- Muir Gordon
- Muir Kenneth
- Mumtaz Faiz
- Murphy Michael
- Murray Alexandra
- Murray Keith W
- Murrell Shirley
- Murtola Teemu
- Muthukumar D
- Naerger Harry
- Namasivayam Siva
- Nargund Vinod
- Nawrocki [Unknown]
- Neal David E
- Neilson Donald
- Nethersell A
- Newby Jacqueline C
- Newman Hugh
- Newton R
- Nielsen Sune F
- Nordestgaard Børge G
- O'Boyle P J
- O'Brien J
- O'Brien Tim S
- O'Donnell H
- O'Donoghue E
- O'Donoghue Neil
- O'Reilly P
- O'Rourke J S
- O'Sullivan Joe
- O'Sullivan Patricia
- Oakley Neil
- Ogden Chris
- Ohja Hemant
- Oliver Tim
- Omara Tracy
- Ong Eng K
- Osborn David
- Ostler Peter
- Owen J
- Palfrey Edward
- Panades Miguel
- Panakis Niki
- Pancharatnam M
- Pandha Hardev
- Pantelides Michalakis L
- Panwar U
- Parikh Omi
- Park Hyun
- Park Jong Y
- Parker Chris
- Parker Christopher H
- Parys Bohdan T
- Pascoe Sarah
- Pashayan Nora
- Patel Anup
- Paterson Joan
- Pathack S
- Pati Jhumur
- Patterson Helen
- Pattu [Unknown]
- Paul A
- Paul Alan
- Paulo Paula
- Payne Heather
- Peake David
- Pedersen John
- Pedley I
- Pengelly A
- Peracha Amjad M
- Perry Matthew
- Persad Raj
- Peters John
- Pharoah Paul
- Philp N H
- Philp T
- Pickering Lisa M
- Pigott Katharine
- Pinto Pedro
- Plail R
- Plowman P Nicholas
- Pocock Richard D
- Pope A J
- Popert Rick
- Popov Elenko
- Porter Tim
- Potter John M
- Pow-Sang Julio
- Powell Christopher
- Powell Philip
- Powles Thomas B
- Prasad Krishna
- Prasad Seshadri Sri
- Prejbisz J W
- Prescott Stephen
- Protheroe Andrew
- Qureshi Khaver N
- Raby Nigel
- Radlein Selina
- Ragavan Narasimhan
- Raju Palaniappa G S
- Ramachandra Prakash B
- Raman R
- Rane Abhay
- Rankin Julia
- Rao Y
- Ratan Hari L
- Ravi Ramachandran
- Ravishankar K
- Read [Unknown]
- Reddy Paul J
- Rimington Peter R
- Rinckleb Antje
- Rincon Maria
- Riska Shaun
- Ritchie Peter A
- Roberts J Trevor
- Robertson Andrew
- Robinson Angus
- Robinson Anne C
- Robinson Lee Q
- Rochester Mark A
- Roder Andreas
- Rogers P B
- Rosario Derek
- Rosenbaum Tomas P
- Rothwell Neil
- Rowbotham Carl
- Rowe [Unknown]
- Rowley Kathryn
- Ruddy Deborah
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- Samanci Ali
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- Sheehan Denise J
- Sherwin Elizabeth
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- Sidek Norma
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- Sinclair Andrew M
- Singh Pravin
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- Slavov Chavdar
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- Smith Michael F
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- Southey Melissa C
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- Sriram Rajagopalan
- Staffurth John N
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- Stattin Paer
- Stegmaier Christa
- Stephens Sarah
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- Stockdale Andrew
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- Stuart Nicholas S A
- Sugden Elaine
- Summerton Duncan
- Sundar Santhanam
- Sundaram S K
- Suresh Gokarakonda
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- Symons Stephanie J
- Syndikus Isabel
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- Taylor John W
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- Toussi Hamid
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- Turner Kevin J
- Turner Megan
- Tweedle James
- Tymrakiewicz Malgorzata
- Tyrell C J
- Umez-Eronini N
- Urwin Graeme H
- Vale Justin A
- Van As [Unknown]
- Van As Nicholas
- Vasanthan Subramaniam
- Vesey Sean
- Vilarino-Varela Maria
- Violet John
- Virdi Jaspal
- Viñuela Ana
- Vlahova Aleksandrina
- Vogel Walther
- Wade Robert
- Wahlfors Tiina
- Waite Katherine
- Walker E M
- Walker Roger
- Wallace David M A
- Wallinder Hans
- Wang Liang
- Watkin Nicholas A
- Watson M E
- Waxman J H
- Waymont Brian
- Weaver Andrew
- Webb Ralph J
- Wedderburn Andrew
- Weischer Maren
- Wells Paula
- Wemyss-Holden G D
- Weston P M T
- Wheatley Duncan
- Whelan P
- Whillis D
- Whitmore Ian
- Wiklund Fredrik
- Wilde Adam D
- Wiles Vicki
- Wilkins Marie
- Wilkinson Rosemary
- Williams John H
- Williams Simon
- Willis Michael
- Wills Michael I
- Wilson J R
- Wilson Richard
- Winkler Mathias H
- Wise Marcus
- Wokozorczyk Dominika
- Wokołorczyk Dominika
- Wood Glenn
- Woodhams Simon
- Woodhouse C
- Woodward Cathryn
- Woolf [Unknown]
- Woolfenden K A
- Worlding Jane
- Wright Mark
- Wu Huihai
- WYLIE [Unknown]
- Wylie James P
- Wynne Chris
- Yeadon Trina
- Zachariah Babu
- Zang Angelika
- Zarkar A
- Zheng Wei
- Publication venue
- 'Oxford University Press (OUP)'
- Publication date
- 01/01/2015
- Field of study
Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have
fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in
25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16
regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of
correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP,
while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in
Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium
(LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region.
Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant
enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the
refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa,
an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of
PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent
signals within the same regio
Whole-genome sequencing reveals host factors underlying critical COVID-19
- Author
- Abd Elghafar M.S.
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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
GRE predictive validity in a Master's program in clinical psychology.
- Author
- Publication venue
- 'American Psychological Association (APA)'
- Publication date
- Field of study
The Behavioral Dynamics of Mutual Responsiveness in Early Face-to-Face Mother-Infant Interactions
- Publication venue
- Scholarship@Western
- Publication date
- 01/12/1987
- Field of study
The behavioral dynamics of 3 different types of early mother-infant interactions were examined. 20 mothers were instructed to play with, imitate, and hold the attention of their 13-16-week-old infants in 3 3-min episodes. Frequency of vocalization, gaze direction, and smiling by both interactants, tactile play by the mother, and crying by the infant were coded from the video-records. Mothers were more talkative, touched their babies more often, showed more positive affect, and were more animated during play and attention-getting than during imitation. Despite these differences in maternal interaction style, infants were equally attentive to their mothers, as measured by gaze, in all 3 conditions. Sequential analyses of changes in behavior were used as indicators of the moment-to-moment responsiveness of the mother and the active involvement of the infant in the interaction. According to these measures, mothers displayed significant levels of actual behavioral responsiveness only in play and imitation episodes, and infants were actively involved only under those same conditions. Furthermore, correlational analyses revealed that the infants of mothers who were most responsive during play and attention-getting episodes also displayed relatively high levels of responsiveness. Further research is necessary to establish and identify the nature of the suggested relation between maternal responsiveness and infant involvement in interaction
Attachment theory and developmental psychology: Canadian contributions and introduction to the special issue.
- Publication venue
- 'American Psychological Association (APA)'
- Publication date
- Field of study
Using Personal Computers for Behavioral Coding in Real-Time: The REALTIME and TMERGE Programs
- Publication venue
- Scholarship@Western
- Publication date
- 01/10/1990
- Field of study