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DEVELOPMENT OF AN ON-LINE, REAL-TIME ALPHA RADIATION RADIATION MONITOR FOR LIQUID STREAMS
- Author
- Publication venue
- 'Office of Scientific and Technical Information (OSTI)'
- Publication date
- 29/12/1995
- Field of study
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.
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- Adamsara A.
- Adanini O.
- Adeleye O.
- Adra D.
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- Afilalo M.
- Afolabi D.
- Afrasiabi Z.
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- Akinkugbe O.
- Aksentijevich A.
- Al-Afghani H.
- Al-Awdah L.
- Alaamery M.
- Alahmadey Z. Z.
- Alaverdian D.
- Alavere H.
- Albader A.
- Albaiceta G. M.
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- AlBardis H.
- Albeladi M.
- Albesher N.
- Albrich W.
- AlDhawi N.
- Aldridge J.
- Aleagha A. E.
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- Almohammed I.
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- Voide C.
- von Frenckell C.
- von Hohenstaufen K. A.
- Vonk J. M.
- Vulesevic B.
- Vuylsteke A.
- Wackett T.
- Wadams B.
- Waddington N.
- Wagstaff V.
- Wain L. V.
- Waite A. A. C.
- Wakefield P.
- Wakinshaw F.
- Waldron J.
- Walker D.
- Walker R.
- Walker S.
- Walker S.
- Wall A.
- Walsh T.
- Walters R. K.
- Walton O.
- Wang B.
- Wang J.
- Wang X.
- Wanying Z.
- Ward G.
- Ward L.
- Ward M.
- Warden S.
- Warmerdam R.
- Warren D.
- Wassall H.
- Wasson C.
- Watkins C.
- Watson E.
- Watson G.
- Watson J.
- Watters M.
- Waugh V.
- Weaver J.
- Webster A.
- Webster D.
- Webster K.
- Wei S.
- Weiss S. T.
- Weldon C. H.
- Wells C.
- Welters I. D.
- Weston H.
- Whileman A.
- Whitbread J.
- White D.
- White I.
- White K.
- White M.
- White N.
- White N.
- Whiteley S.
- Whiteside J.
- Whittle H.
- Whitton C.
- Whyte C.
- Wicks S. J.
- Wilby E.
- Wilcox L.
- Wilcox R.
- Wild H.
- Wild L.
- Wiles M.
- Wilkins J.
- Wilkinson A.
- Wilkinson B.
- Willer C.
- Williams A.
- Williams A.
- Williams A.
- Williams A. T.
- Williams D.
- Williams E.
- Williams F.
- Williams G.
- Williams H.
- Williams K.
- Williams M.
- Williams P.
- Williams S.
- Williams T.
- Willis C.
- Willis H.
- Wills M.
- Willson J.
- Wilson A.
- Wilson D. J.
- Wilson J.
- Wilson J. F.
- Winnard S.
- Winter-Goodwin B.
- Wolf-Roberts R.
- Wolford B.
- Wong J.
- Wood D.
- 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
Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.
- Author
- Aarsland D
- Abramzon Y
- Adams DJ
- Adeleye A
- Aguilar M
- Ahmed S
- Al-Chalabi A
- Al-Sarraj S
- Al-Sarraj S
- Alba C
- Alba C
- Albani D
- Albert MS
- Altschuler S
- Alvarez I
- Amar K
- Ambrose JC
- Archibald N
- Arcila-Londono X
- Arepalli S
- Aronica E
- Arumugam P
- Asress S
- Atassi N
- Attems J
- Auluck P
- Baas F
- Baas F
- Babu S
- Bacikova D
- Bacikova D
- Baloh RH
- Baloh RH
- Bandmann O
- Baple EL
- Barrett MJ
- Beach TG
- Bekris LM
- Bennett DA
- Benussi L
- Berry JD
- Bertolin C
- Besser LM
- Bigio EH
- Binetti G
- Black SE
- Blair IP
- Bleda M
- Boada M
- Boardman-Pretty F
- Boeve BF
- Bohannan RC
- Boissiere JM
- Borroni B
- Boustred CR
- Bowser R
- Bowser R
- Boylan KB
- Brady CB
- Brett F
- Brice A
- Brice A
- Brittain H
- Broach J
- Broach JR
- Broce I
- Brown RH
- Brunetti M
- Bruni A
- Butovsky O
- Calini D
- Calvo A
- Camu W
- Canosa A
- Capps E
- Caraway CA
- Caroppo P
- Castellotti B
- Caulfield MJ
- Cereda C
- Ceroni M
- Chan GC
- Chandran S
- Chia R
- Chiang H-H
- Chiò A
- Chiò A
- Church A
- Clarimon J
- Clarimon J
- Coebergh J
- Colombrita C
- Comi GP
- Cooper-Knock J
- Corcia P
- Corrado L
- Corti S
- Costantini A
- Cox GA
- Craig CEH
- Crary J
- Critchley P
- Dalgard CL
- Danek A
- Danielson EW
- Dardiotis E
- Daugherty LC
- De Belleroche J
- De Burca A
- Del Bo R
- Devereau A
- Dewan R
- Dickson D
- Diehl-Schimd J
- Diekstra FP
- Diez-Fairen M
- Diez-Fairen M
- Ding J
- Dols-Icardo O
- Drepper C
- Drory V
- Drory VE
- Dubnau J
- Duga S
- Dunckley TL
- Duyckaerts C
- D’Alfonso S
- Elgar G
- Esteban-Pérez J
- Faber K
- Faghri F
- Fallini C
- Farren J
- Feldman E
- Ferman T
- Ferrari R
- Ferrucci L
- Finkbeiner S
- Flanagan ME
- Floeter MK
- Floris G
- Foroud TM
- Fortea J
- Foulger RE
- Fowler T
- Fraenkel E
- Fratta P
- Fratta P
- Furió-Tarí P
- Gagliardi S
- Galimberti D
- Gan-Or Z
- García-Redondo A
- Gellera C
- Gentleman S
- Gerhard G
- Ghetti B
- Ghidoni R
- Ghosh BCP
- Gibbs JR
- Gibbs JR
- Gibson SB
- Gkazi AS
- Glass JD
- Goate A
- Goldstein D
- González-Aramburu I
- Gotkine M
- Goutman SA
- Graff C
- Graff-Radford NR
- Hackett JM
- Halai D
- Hamblin A
- Hammell MG
- Hardiman O
- Hardy JA
- Harms M
- Harms MB
- Harris B
- Heiman-Patterson T
- Heiman-Patterson TD
- Henderson S
- Hernandez DG
- Hernández I
- Hickman RA
- Hjermind LE
- Hodges AK
- Holman JE
- Hoover B
- Hornstein E
- Hu H-C
- Hu MTM
- Hubbard TJP
- Hupalo D
- Hupalo DN
- Ibáñez K
- Illán-Gala I
- Infante J
- Iranzo A
- Jabbari E
- Jackson R
- Jansson L
- Johansson PM
- Jones LJ
- Kaiser SM
- Kamel F
- Kasperaviciute D
- Kaufmann H
- Kayikci M
- Keagle P
- Keith J
- Kenna KP
- Khoshnood B
- Kim RC
- King A
- Kirby J
- Klein G
- Kobylecki C
- Kost J
- Kowal N
- Kowall NW
- Krüger R
- Kukull W
- Kuzma A
- Kwan J
- Laaksovirta H
- Lage C
- Lahnstein L
- Landers JE
- Landi F
- Lange DJ
- Lauria G
- Lawson K
- Le Ber I
- Leblond-Manry C
- Lee EB
- Leigh PN
- Leigh SEA
- Leong IUS
- Lesage S
- Leverenz JB
- Lewis EA
- Lleó A
- Lleó A
- Logroscino G
- Lopez G
- Lopez JF
- Love S
- Lumbroso S
- MacGowan DJ
- MacGowan DJL
- Malaspina A
- Maleady-Crowe F
- Mann C
- Mao Q
- Maragakis NJ
- Marti MJ
- Martinez EM
- Martinez-McGrath E
- Masellis M
- Masliah E
- Mason J
- Massey LA
- May P
- Mazzini L
- McDonagh EM
- McKeith I
- McKenna-Yasek D
- McLaughlin RL
- McMillan C
- Menon V
- Mesulam M-M
- Miller JW
- Miller TM
- Molina-Porcel L
- Monuki ES
- Mora G
- Moreno-Grau S
- Morris CM
- Morris CM
- Morris HR
- Morris HR
- Morrison KE
- Moutsianas L
- Mouzat K
- Mueller M
- Murugaesu N
- Muñoz-Blanco JL
- Myllykangas L
- Nacmias B
- Nalls MA
- Nath A
- Nath U
- Need AC
- Newell KL
- Nicholson GA
- Nielsen JE
- Nilsson CF
- Norcliffe-Kaufmann L
- Novelli V
- Odhams CA
- Orrell RW
- Ostrow LW
- Ostrow LW
- Padovani A
- Paganoni S
- Pal S
- Pall H
- Palma J-A
- Palmer L
- Pamphlett R
- Pastor P
- Pastor P
- Patch C
- Patsopoulos NA
- Pavese N
- Paviour D
- Pensato V
- Perez-Gil D
- Perkins M
- Perneczky R
- Phatnani H
- Phillips-Cremins J
- Pickering-Brown S
- Pioro E
- Pletnikova O
- Polak M
- Pollard HB
- Polychronopoulos D
- Portley MK
- Poss M
- Puca AA
- Pullinger J
- Pulst SM
- Querin G
- Rademakers R
- Rahim T
- Raj T
- Ratti A
- Ravits J
- Ravits JM
- Rendon A
- Renton AE
- Renton AE
- Resnick SM
- Reynolds RH
- Riesgo-Ferreiro P
- Robberecht W
- Robey I
- Rodríguez-Rodríguez E
- Rogaeva E
- Rogaeva E
- Rogaeva E
- Rogers T
- Rohrer JD
- Ross OA
- Rossi G
- Rossi M
- Rothstein JD
- Rouleau GA
- Rowe JB
- Ruiz A
- Ryten M
- Sabir MS
- Sanchez-Juan P
- Sapp PC
- Sareen D
- Savage K
- Sawant K
- Scarpini E
- Scherzer CR
- Schlachetzki JC
- Scholz SW
- Scott RH
- Scotter EL
- Sendtner M
- Serpente M
- Serrano GE
- Shakkottai V
- Shalem O
- Shankaracharya FNU
- Sharma J
- Shaw CE
- Shaw PJ
- Shaw PJ
- Shneider NA
- Siddiq A
- Sidle KC
- Sidransky E
- Sieghart A
- Silani V
- Simmons Z
- Simmons Z
- Singleton AB
- Smedley D
- Smith BN
- Smith C
- Smith KR
- Soltis AR
- Sorarù G
- Sorbi S
- Sosinsky A
- Spooner W
- Stefanis L
- Stein TD
- Stevens HE
- Stevic Z
- Stone DJ
- Stuckey A
- Sukumar G
- Sultana R
- Tagliavini F
- Talbot K
- Tanaka T
- Taroni F
- Tayebi N
- Ten Asbroek ALMA
- Thomas AJ
- Thomas ERA
- Thompson LM
- Thompson SR
- Ticozzi N
- Tienari PJ
- Tilley BS
- Tiloca C
- Topp SD
- Torkamani A
- Traynor BJ
- Tregidgo C
- Troakes C
- Troakes C
- Trojanowski JQ
- Troncoso JC
- Troncoso JC
- Tucci A
- Tuck M
- Turner MR
- Valori M
- Van Blitterswijk M
- Van Damme P
- Van Deerlin V
- Van den Berg LH
- Van Den Bosch L
- Van Rheenen W
- Vance C
- Vaughan J
- Veldink JH
- Viollet C
- Vonsattel JP
- Waldo ML
- Walsh E
- Walton RL
- Watters SA
- Welland MJ
- Wilkerson MD
- Williams E
- Williams KL
- Witkowska K
- Woltjer R
- Wood SM
- Wszolek ZK
- Wu L
- Wu Z
- Xiromerisiou G
- Zaitlen N
- Zarowiecki M
- Zecca C
- Zhang B
- Zhang X
- Zinman L
- Öijerstedt L
- Publication venue
- Neuron
- Publication date
- 01/01/2020
- Field of study
We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered
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
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- S Rose
- S Rundell
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- S Sathe
- S Selvanayagam
- S Shelton
- S Shepardson
- S Siddiqui
- S Smuts
- S Sousa Arias
- S Spencer
- S Srikaran
- S Stone
- S Swann
- S Tilbey
- S Turki
- S Turney
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- S Wadd
- S Whiteley
- S Williams
- S Wood
- S Yussuf
- Sabino Scolletta
- Samreen Ijaz
- Sandro Mancarella
- Sandro Panese
- Sara Amitrano
- Sara McDonald
- Sarah Law
- Sarah McCafferty
- Saverio Giuseppe Parisi
- Saye Khoo
- Scott Richard
- Semple Malcolm G
- Serafina Valente
- Serena Ludovisi
- Sergio Daga
- Seán Keating
- Shankar-Hari Manu
- Shen Xia
- Shih Barbara
- Shiranee Sriskandan
- Shona C Moore
- Silvia Cappelli
- Simona Marcantonio
- Simone Furini
- Sophie Halpin
- 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
- T Cosier
- T Coventry
- T Duncan
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- T Hazleton
- 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
Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.
- Author
- Charaka Hadinnapola
- Marta Bleda
- Matthias Haimel
- Nicholas Screaton
- Andrew Swift
- Peter Dorfmüller
- Stephen D. Preston
- Mark Southwood
- Jules Hernandez-Sanchez
- Jennifer Martin
- Carmen Treacy
- Katherine Yates
- Harm Bogaard
- Colin Church
- Gerry Coghlan
- Robin Condliffe
- Paul A. Corris
- Simon Gibbs
- Barbara Girerd
- Simon Holden
- Marc Humbert
- David G. Kiely
- Allan Lawrie
- Rajiv Machado
- Robert MacKenzie Ross
- Shahin Moledina
- David Montani
- Michael Newnham
- Andrew Peacock
- Joanna Pepke-Zaba
- Paula Rayner-Matthews
- Olga Shamardina
- Florent Soubrier
- Laura Southgate
- Jay Suntharalingam
- Mark Toshner
- Richard Trembath
- Anton Vonk Noordegraaf
- Martin R. Wilkins
- Stephen J. Wort
- John Wharton
- Stefan Gräf
- Nicholas W. Morrell
- Timothy Aitman
- David Bennett
- Mark Caulfield
- Patrick Chinnery
- Daniel Gale
- Ania Koziell
- Taco W Kuijpers
- Michael A Laffan
- Eamonn Maher
- Hugh S Markus
- Willem H Ouwehand
- David Perry
- F Lucy Raymond
- Irene Roberts
- Kenneth Smith
- Adrian Thrasher
- Hugh Watkins
- Catherine Williamson
- Geoffrey Woods
- Sofie Ashford
- John R Bradley
- Debra Fletcher
- Tracey Hammerton
- Roger James
- Nathalie Kingston
- Willem H Ouwehand
- Christopher J Penkett
- F Lucy Raymond
- Kathleen Stirrups
- Marijke Veltman
- Tim Young
- Sofie Ashford
- Matthew Brown
- Naomi Clements-Brod
- John Davis
- Eleanor Dewhurst
- Marie Erwood
- Amy Frary
- Rachel Linger
- Sofia Papadia
- Karola Rehnstrom
- Hannah Stark
- David Allsup
- Steve Austin
- Tamam Bakchoul
- Tadbir K Bariana
- Paula Bolton-Maggs
- Elizabeth Chalmers
- Peter Collins
- Wendy N Erber
- Tamara Everington
- Remi Favier
- Kathleen Freson
- Bruce Furie
- Michael Gattens
- Keith Gomez
- Daniel Greene
- Andreas Greinacher
- Daniel Hart
- Johan WM Heemskerk
- Yvonne Henskens
- Rashid Kazmi
- David Keeling
- Anne M Kelly
- Michael A Laffan
- Michele P Lambert
- Claire Lentaigne
- Ri Liesner
- Sarah Mangles
- Mary Mathias
- Carolyn M Millar
- Andrew Mumford
- Paquita Nurden
- Willem H Ouwehand
- Sofia Papadia
- Jeanette Payne
- John Pasi
- David J Perry
- Kathelijne Peerlinck
- Michael Richards
- Matthew Rondina
- Catherine Roughley
- Sol Schulman
- Harald Schulze
- Marie Scully
- Suthesh Sivapalaratnam
- R Campbell Tait
- Kate Talks
- Jecko Thachil
- Ernest Turro
- Cheng-Hock Toh
- Chris Van Geet
- Minka De Vries
- Timothy Q Warner
- Sarah Westbury
- Abigail Furnell
- Rutendo Mapeta
- Ilenia Simeoni
- Simon Staines
- Jonathan Stephens
- Kathleen Stirrups
- Deborah Whitehorn
- Christopher Watt
- Antony Attwood
- Louise Daugherty
- Sri VV Deevi
- Csaba Halmagyi
- Fengyuan Hu
- Roger James
- Vera Matser
- Stuart Meacham
- Karyn Megy
- Christopher J Penkett
- Kathleen Stirrups
- Catherine Titterton
- Salih Tuna
- Ping Yu
- Julie von Ziegenweldt
- William Astle
- Keren Carss
- Daniel Greene
- Hana Lango-Allen
- Ernest Turro
- William Astle
- Daniel Greene
- Sylvia Richardson
- Ernest Turro
- Paul Calleja
- Stuart Rankin
- Wojciech Turek
- Christine Bryson
- Julie Anderson
- Debra Fletcher
- Coleen McJannet
- Sophie Stock
- Tim Young
- Evangeline Wassmer
- Aman Sohal
- Saikat Santra
- Julie Vogt
- Manali Chitre
- Deepa Krishnakumar
- Gautum Ambegaonkar
- Anna Maw
- Ruth Armstrong
- Soo-Mi Park
- Sarju Mehta
- Joan Paterson
- Jenny Carmichael
- Louise Allen
- Anke Hensiek
- Helen Firth
- Penelope Stein
- Patrick Deegan
- Rainer Doffinger
- Alasdair Parker
- Maria Bitner-Glindzicz
- Richard Scott
- Jane Hurst
- Elisabeth Rosser
- Melissa Lees
- Emma Clement
- Robert Henderson
- Dorothy Thompson
- Alice Gardham
- Paul Gissen
- Dragana Josifova
- Ellen Thomas
- Chris Patch
- Charu Deshpande
- Frances Flinter
- Muriel Holder
- Natalie Canham
- Emma Wakeling
- Susan Holder
- Neeti Ghali
- Angie Brady
- Virginia Clowes
- Robert MacLaren
- Andrew Webster
- Anthony Moore
- Gavin Arno
- Michel Michaelides
- Julia Rankin
- Manju Kurian
- Elaine Murphy
- Keren Carss
- Alba Sanchis-Juan
- Marie Erwood
- Eleanor Dewhurst
- Detelina Grozeva
- F Lucy Raymond
- Evan Reid
- Geoff Woods
- Marc Tischkowitz
- Richard Sandford
- Sonia Ali
- Amanda Creaser-Myers
- Victoria Cookson
- Rosa DaCosta
- Natalie Dormand
- Pavandeep K Ghataorhe
- Alan Greenhalgh
- Anna Huis in’t Veld
- Fiona Kennedy
- Rob Mackenzie Ross
- Larahmie Masati
- Sharon Meehan
- Shokri Othman
- Val Pollock
- Gary Polwarth
- Christopher J Rhodes
- Kevin Rue-Albrecht
- Gwen Schotte
- Debbie Shipley
- Yvonne Tan
- Ivy Wanjiku
- John Wort
- Kenneth Smith
- Taco Kuijpers
- Adrian Thrasher
- James Thaventhiran
- Matthew Brown
- Hana Lango Allen
- Ilenia Simeoni
- Emily Staples
- Crina Samarghitean
- Hana Alachkar
- Richard Antrobus
- Gururaj Arumugakani
- Chiara Bacchelli
- Helen Baxendale
- Claire Bethune
- Shahnaz Bibi
- Claire Booth
- Michael Browning
- Siobhan Burns
- Anita Chandra
- Nichola Cooper
- Sophie Davies
- Lisa Devlin
- Rainer Doffinger
- Elizabeth Drewe
- David Edgar
- William Egner
- Rohit Ghurye
- Kimberley Gilmour
- Sarah Goddard
- Pavel Gordins
- Sofia Grigoriadou
- Scott Hackett
- Rosie Hague
- Grant Hayman
- Archana Herwadkar
- Aarnoud Huissoon
- Stephen Jolles
- Peter Kelleher
- Dinakantha Kumararatne
- Sara Lear
- Hilary Longhurst
- Lorena Lorenzo
- Jesmeen Maimaris
- Ania Manson
- Elizabeth McDermott
- Sai Murng
- Sergey Nejentsev
- Sadia Noorani
- Eric Oksenhendler
- Mark Ponsford
- Waseem Qasim
- Isabella Quinti
- Alex Richter
- Ravishankar Sargur
- Sinisa Savic
- Suranjith Seneviratne
- Carrock Sewell
- Hans Stauss
- Moira Thomas
- Steve Welch
- Lisa Willcocks
- Nigel Yeatman
- Patrick Yong
- null null
- Publication venue
- American Heart Association
- Publication date
- 01/01/2017
- Field of study
BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation
Comprehensive Cancer-Predisposition Gene Testing in an Adult Multiple Primary Tumor Series Shows a Broad Range of Deleterious Variants and Atypical Tumor Phenotypes.
- Author
- Adlard Julian
- Ahmed Munaza
- Aitman Timothy
- Alachkar Hana
- Ali Sonia
- Allen Hana Lango
- Allen Louise
- Allsup David
- Ambegaonkar Gautum
- Anderson Julie
- Antrobus Richard
- Armstrong Ruth
- Armstrong Ruth
- Arno Gavin
- Arumugakani Gururaj
- Ashford Sofie
- Ashford Sofie
- Astle William
- Attwood Antony
- Austin Steve
- Bacchelli Chiara
- Bakchoul Tamam
- Bariana Tadbir K.
- Barwell Julian
- Baxendale Helen
- Bennett David
- Bethune Claire
- Bibi Shahnaz
- Bitner-Glindzicz Maria
- Bleda Marta
- Boggard Harm
- Bolton-Maggs Paula
- Booth Claire
- Bradley John R.
- Brady Angie
- Brewer Carole
- Brown Matthew
- Browning Michael
- Bryson Christine
- Burns Siobhan
- Calleja Paul
- Canham Natalie
- Carmichael Jenny
- Carss Keren
- Carss Keren
- Casey Ruth T.
- Caulfield Mark
- Chalmers Elizabeth
- Chandra Anita
- Chen-Shtoyerman Rakefet
- Chinnery Patrick
- Chitre Manali
- Church Colin
- Clark Graeme
- Clement Emma
- Clements-Brod Naomi
- Clowes Virginia
- Coghlan Gerry
- Cole Trevor
- Collins Peter
- Cookson Victoria
- Cooper Nichola
- Corris Paul
- Creaser-Myers Amanda
- DaCosta Rosa
- Daugherty Louise
- Davies Sophie
- Davis John
- De Vries Minka
- Deegan Patrick
- Deevi Sri V.V.
- Deshpande Charu
- Devlin Lisa
- Dewhurst Eleanor
- Dixon Peter
- Doffinger Rainer
- Dormand Natalie
- Drewe Elizabeth
- Edgar David
- Egner William
- Erber Wendy N.
- Erwood Marie
- Erwood Marie
- Evans Dafydd Gareth
- Everington Tamara
- Favier Remi
- Firth Helen
- Fletcher Debra
- Flinter Frances
- Fostira Florentia
- Frary Amy
- Freson Kathleen
- Furie Bruce
- Furnell Abigail
- Gale Daniel
- Gardham Alice
- Gattens Michael
- Ghali Neeti
- Ghataorhe Pavandeep K.
- Ghurye Rohit
- Gibbs Simon
- Gilmour Kimberley
- Gissen Paul
- Goddard Sarah
- Gomez Keith
- Gordins Pavel
- Graf Stefan
- Greene Daniel
- Greenhalgh Alan
- Greenhalgh Lynn
- Greinacher Andreas
- Grigoriadou Sofia
- Grozeva Detelina
- Gräf Stefan
- Hackett Scott
- Hadinnapola Charaka
- Hague Rosie
- Haimel Matthias
- Halmagyi Csaba
- Hammerton Tracey
- Hanson Helen
- Hart Daniel
- Hayman Grant
- Heemskerk Johan W.M.
- Henderson Alex
- Henderson Robert
- Hensiek Anke
- Henskens Yvonne
- Herwadkar Archana
- Hoffman Jonathan
- Holden Simon
- Holder Muriel
- Holder Susan
- Hu Fengyuan
- Huis in?t Veld Anna
- Huissoon Aarnoud
- Humbert Marc
- Hurst Jane
- Izatt Louise
- James Roger
- Jolles Stephen
- Josifova Dragana
- Kazmi Rashid
- Keeling David
- Kelleher Peter
- Kelly Anne M.
- Kennedy Fiona
- Kiely David
- Kingston Nathalie
- Koziell Ania
- Krishnakumar Deepa
- Kuijpers Taco
- Kuijpers Taco W.
- Kumar Ajith
- Kumararatne Dinakantha
- Kurian Manju
- Kwong Ava
- Laffan Michael A.
- Lalloo Fiona
- Lambert Michele P.
- Lango-Allen Hana
- Lawrie Allan
- Lear Sara
- Lees Melissa
- Lentaigne Claire
- Liesner Ri
- Linger Rachel
- Longhurst Hilary
- Lorenzo Lorena
- Louka Eleni
- Luchetti Andrea
- Machado Rajiv
- MacLaren Robert
- Maher Eamonn
- Maher Eamonn R.
- Maimaris Jesmeen
- Mangles Sarah
- Manson Ania
- Mapeta Rutendo
- Mapeta Rutendo
- Markus Hugh S.
- Martin Jennifer
- Martin Jose-Ezequiel
- Masati Larahmie
- Mathias Mary
- Matser Vera
- Maw Anna
- McDermott Elizabeth
- McJannet Coleen
- Meacham Stuart
- Meehan Sharon
- Megy Karyn
- Megy Karyn
- Mehta Sarju
- Michaelides Michel
- Millar Carolyn M.
- Moledina Shahin
- Moore Anthony
- Morrell Nicholas
- Mumford Andrew
- Murng Sai
- Murphy Elaine
- Nejentsev Sergey
- Noorani Sadia
- Nurden Paquita
- Oksenhendler Eric
- Ong Kai Ren
- Othman Shokri
- Ouwehand Willem H.
- Ouwehand Willem H.
- Papadia Sofia
- Park Soo-Mi
- Park Soo-Mi
- Parker Alasdair
- Pasi John
- Patch Chris
- Paterson Joan
- Paterson Joan
- Payne Jeanette
- Peacock Andrew
- Peerlinck Kathelijne
- Penkett Chris
- Penkett Christopher J.
- Pepke-Zaba Joanna
- Perry David
- Perry David J.
- Pollock Val
- Polwarth Gary
- Ponsford Mark
- Qasim Waseem
- Quinti Isabella
- Rankin Julia
- Rankin Stuart
- Raymond F. Lucy
- Rayner-Matthews Paula
- Rehnstrom Karola
- Reid Evan
- Rhodes Christopher J.
- Richards Michael
- Richardson Sylvia
- Richter Alex
- Roberts Irene
- Rodger Faye
- Rondina Matthew
- Ross Rob Mackenzie
- Rosser Elisabeth
- Roughley Catherine
- Roy Noémi
- Rue-Albrecht Kevin
- Samarghitean Crina
- Sanchis-Juan Alba
- Sandford Richard
- Santra Saikat
- Sargur Ravishankar
- Savic Sinisa
- Schotte Gwen
- Schulman Sol
- Schulze Harald
- Scott Richard
- Scully Marie
- Searle Claire
- Seneviratne Suranjith
- Sewell Carrock
- Shakeel Hassan
- Shamardina Olga
- Shipley Debbie
- Side Lucy
- Simeoni Ilenia
- Sivapalaratnam Suthesh
- Skytte Anne-Bine
- Smith Kenneth G.C.
- Smith Philip S.
- Snape Katie
- Sohal Aman
- Southgate Laura
- Staines Simon
- Staples Emily
- Stark Hannah
- Stauss Hans
- Stein Penelope
- Stephens Jonathan
- Stephens Jonathan
- Stirrups Kathleen
- Stirrups Kathleen
- Stock Sophie
- Suntharalingam Jay
- Talks Kate
- Tan Yvonne
- Thachil Jecko
- Thaventhiran James
- Thomas Ellen
- Thomas Moira
- Thompson Dorothy
- Thrasher Adrian
- Tischkowitz Marc
- Tischkowitz Marc D.
- Titterton Catherine
- Toh Cheng-Hock
- Toshner Mark
- Treacy Carmen
- Trembath Richard
- Tuna Salih
- Turek Wojciech
- Turro Ernest
- Van Geet Chris
- Veltman Marijke
- Vogt Julie
- von Ziegenweldt Julie
- Vonk Noordegraaf Anton
- Wakeling Emma
- Wanjiku Ivy
- Warner Timothy Q.
- Wassmer Evangeline
- Watkins Hugh
- Watt Christopher
- Webster ndrew
- Welch Steve
- West Hannah
- Westbury Sarah
- Wharton John
- Whitehorn Deborah
- Whitworth James
- Wilkins Martin
- Willcocks Lisa
- Williamson Catherine
- Woods Geoff
- Woods Geoffrey
- Woodward Emma R.
- Wort John
- Yeatman Nigel
- Yong Patrick
- Young Tim
- Yu Ping
- Publication venue
- Am J Hum Genet
- Publication date
- 01/01/2018
- Field of study
Multiple primary tumors (MPTs) affect a substantial proportion of cancer survivors and can result from various causes, including inherited predisposition. Currently, germline genetic testing of MPT-affected individuals for variants in cancer-predisposition genes (CPGs) is mostly targeted by tumor type. We ascertained pre-assessed MPT individuals (with at least two primary tumors by age 60 years or at least three by 70 years) from genetics centers and performed whole-genome sequencing (WGS) on 460 individuals from 440 families. Despite previous negative genetic assessment and molecular investigations, pathogenic variants in moderate- and high-risk CPGs were detected in 67/440 (15.2%) probands. WGS detected variants that would not be (or were not) detected by targeted resequencing strategies, including low-frequency structural variants (6/440 [1.4%] probands). In most individuals with a germline variant assessed as pathogenic or likely pathogenic (P/LP), at least one of their tumor types was characteristic of variants in the relevant CPG. However, in 29 probands (42.2% of those with a P/LP variant), the tumor phenotype appeared discordant. The frequency of individuals with truncating or splice-site CPG variants and at least one discordant tumor type was significantly higher than in a control population (χ2 = 43.642; p ≤ 0.0001). 2/67 (3%) probands with P/LP variants had evidence of multiple inherited neoplasia allele syndrome (MINAS) with deleterious variants in two CPGs. Together with variant detection rates from a previous series of similarly ascertained MPT-affected individuals, the present results suggest that first-line comprehensive CPG analysis in an MPT cohort referred to clinical genetics services would detect a deleterious variant in about a third of individuals.JW is supported by a Cancer Research UK Cambridge Cancer Centre Clinical Research Training Fellowship. Funding for the NIHR BioResource – Rare diseases project was provided by the National Institute for Health Research (NIHR, grant number RG65966). ERM acknowledges support from the European Research Council (Advanced Researcher Award), NIHR (Senior Investigator Award and Cambridge NIHR Biomedical Research Centre), Cancer Research UK Cambridge
Cancer Centre and Medical Research Council Infrastructure Award. The
University of Cambridge has received salary support in respect of EM from the NHS in the East of England through the Clinical Academic Reserve. The views expressed are those of the authors and not necessarily those of the NHS or Department of Health. DGE is an NIHR Senior Investigator and is supported by the all Manchester NIHR Biomedical Research Centre
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.
- Agrawal S.
- Agüero D.
- Ahmad N.
- Ahmadi S.
- Ahmed A.
- Ahmed C.
- Akeroyd L.
- Akhtar M.N.
- Akinkugbe O.
- Aksentijevich A.
- Al Harthi F.
- Al Mutairi 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.
- Almaden-Boyle C.
- 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.
- Arias S.S.
- Arif S.
- Armstrong J.
- Armstrong L.
- Armstrong R.
- Arning N.
- Arnold S.
- Arranz M.J.
- Arribas E.
- Artuso R.
- Arumugam P.
- Arumugam P.
- Ascolillo S.
- Ashraf S.
- Ashton L.
- Aslibekyan S.
- Astin-Chamberlain R.
- Atkinson E.G.
- Attwood B.
- Aucella F.
- Auld D.
- Auld F.
- Austin K.
- Austin P.
- Auton A.
- Ayers A.
- Azarzar S.
- Bachetti T.
- Baikady R.R.
- Baillie J.K.
- Baillie J.K.
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- Baines B.
- Baines D.
- Baines K.
- Baird Y.
- Bakthavatsalam D.
- Balaconis M.K.
- Baldassarri M.
- Ball C.A.
- Baltzell A.H.
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- Zhao J.H.
- Zheng C.
- Zhou W.
- Zitter L.
- Zlatopolsky M.
- Zongo O.
- Zucchi P.
- Zyndorf M.
- 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
GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements
- Author
- Adlard Julian
- Ahmed Munaza
- Aich Anshul
- Aitman Tim
- Alachkar Hana
- Alle Hana Lango
- Allsup David
- Almeida-King Jeff
- Ambrose J. C.
- Amin Aliya S.
- Ancliff Philip
- Antrobus Richard
- Armstrong Ruth
- Arno Gavin
- Arumugam P.
- Ashford Sofie
- Astle William
- Attwood Anthony
- Babbs Chris
- Bakchoul Tamam
- Bariana Tadbir
- Barwell Julian
- Bennett David
- Bentley David
- Bevers R.
- Bierzynska Agnieszka
- Biss Tina
- Bleda M.
- Bleda Marta
- Boardman-Pretty F.
- Bogaard Harm
- Bourne Christian
- Boustred C. R.
- Boyce Sara
- Bradley John
- Breen Gerome
- Brennan Paul
- Brewer Carole
- Brittain H.
- Brod Naomi Clements
- Brown M. A.
- Brown Matthew
- Browning Michael
- Buchan Rachel
- Buckland Matthew
- Bueser Teofila
- Burns Siobhan
- Burren Oliver
- Calleja Paul
- Carr-White Gerald
- Carss Keren
- Casey Ruth
- Caulfield M. J.
- Caulfield Mark
- Cebola Inês
- Chambers Jennifer
- Chambers Jenny
- Chambers John
- Chan G. C.
- Chan Melanie M. Y.
- Cheng Floria
- Chinnery Patrick F.
- Christian Martin
- Church Colin
- Coghlan Gerry
- Colby Elizabeth
- Cole Trevor
- Collins Janine
- Collins Peter
- Colombo Camilla
- Condliffe Robin
- Cook Stuart
- Cook Terry
- Cooley Sharon
- Cooper Nichola
- Corris Paul
- Crisp-Hihn Abigail
- Curry Nicola
- Danesino Cesare
- Daniels Matthew
- Daugherty Louise
- Davis John
- Deevi Sri V. V.
- Dent Timothy
- Dewhurst Eleanor
- Dixon Peter
- Dixon Peter H.
- Donnelly Jennifer
- Downes Kate
- Drazyk Anna
- Drewe Elizabeth
- Dutt Tina
- Edgar David
- Edwards Karen
- Egner William
- Erber Wendy
- Erwood Marie
- Estiu Maria C.
- Estiu Maria Cecilia
- Evans Dafydd Gareth
- Evans Gillian
- Everington Tamara
- Eyries Mélanie
- Favier Remi
- Fletcher Debra
- Fowler T.
- Fox James
- Frary Amy
- French Courtney
- Freson Kathleen
- Frontini Mattia
- Gale Daniel
- Gale Daniel P.
- Gall Henning
- Geary Michael
- Geoghegan Claire
- Gerighty Terry
- Ghio Stefano
- Ghofrani Hossein-Ardeschir
- Gibbs Simon
- Giess A.
- Gilmour Kimberley
- Girerd Barbara
- Goddard Sarah
- Gomez Keith
- Gordins Pavels
- Gosal David
- Grassi Luigi
- Greene Daniel
- Greenhalgh Lynn
- Greinacher Andreas
- Gresele Paolo
- Griffiths Philip
- Grigoriadou Sofia
- Grocock Russell
- Grozeva Detelina
- Gräf Stefan
- Hackett Scott
- Hadinnapola Charaka
- Hague William
- Hague William M.
- Haimel Matthias
- Hall Matthew
- Hamblin A.
- Hanson Helen
- Harkness Kirsty
- Harper Andrew
- Harris Claire
- Hart Daniel
- Hassan Ahamad
- Hayman Grant
- Henderson Alex
- Henderson S.
- Hoffmann Jonathan
- Horvath Rita
- Houweling Arjan
- Howard Luke
- Hu Fengyuan
- Hubbard T. J. P.
- Hudson Gavin
- Hughes Joseph
- Huissoon Aarnoud
- Humbert Marc
- Humphray Sean
- Hunter Sarah
- Hurles Matthew
- Izatt Louise
- Jackson R.
- James Roger
- Johnson Sally
- Jolles Stephen
- Jolley Jennifer
- Jones L. J.
- Jurkute Neringa
- Kasanicki Mary
- Kasperaviciute D.
- Kayikci M.
- Kazkaz Hanadi
- Kazmi Rashid
- Kelleher Peter
- Kiely David
- Kingston Nathalie
- Klima Robert
- Kostadima Myrto
- Kousathanas A.
- Kovacs Gabor
- Koziell Ania
- Kreuzhuber Roman
- Kuijpers Taco
- Kumar Ajith
- Kumararatne Dinakantha
- Kuria Manju
- Laffa Michael
- Lahnstein L.
- Lalloo Fiona
- Lamber Michele
- Lawrie Allan
- Layton Mark
- Leigh S. E. A.
- Lentaigne Claire
- Leong I. U. S.
- Levine Adam
- Levine Adam P.
- Linger Rachel
- Longhurst Hilary
- Lopez F. J.
- Louka Eleni
- Madan Bella
- Maher Eamonn
- Maimaris Jesmeen
- Maleady-Crowe F.
- Mangles Sarah
- Mapeta Rutendo
- Marchbank Kevin
- Marks Stephen
- Markus Hugh S.
- Marschall Hanns-Ulrich
- Marshall Andrew
- Martin Jennifer
- Mathias Mary
- Matthews Emma
- Maude Hannah
- Maxwell Heather
- McAlinden Paul
- McCarthy Mark
- McEntagart M.
- Meacham Stuart
- Mead Adam
- Megy Karyn
- Mehta Sarju
- Michaelides Michel
- Millar Carolyn
- Minneci F.
- Mitchell Alice L.
- Moledina Shahin
- Montani David
- Moor Tony
- Morrell Nicholas
- Moutsianas L.
- Mozere Monika
- Mueller M.
- Muir Keith
- Mumford Andrew
- Murugaesu N.
- Need A. C.
- Newnham Michael
- Nicolaides Kypros
- Noordegraaf Anton Vonk
- O'Donovan P.
- O'Sullivan Jennifer
- Obaji Samya
- Odhams C. A.
- Okoli Steven
- Olschewski Andrea
- Olschewski Horst
- Ong Kai Ren
- Ormondroy Elizabeth
- Ouwehan Willem
- Papadi Sofia
- Park Soo-Mi
- Parry David
- Patch C.
- Paterson Joan
- Peacock Andrew
- Peden John
- Peerlinck Kathelijne
- Penkett Christopher
- Pepke-Zaba Joanna
- Pereira M. B.
- Perez-Gil D.
- Petersen Romina
- Pullinger J.
- Pyle Angela
- Rahim T.
- Rankin Stuart
- Rao Anupama
- Raymond F. Lucy
- Rayner-Matthew Paula
- Rees Christine
- Rendon A.
- Rendon Augusto
- Renton Tara
- Rice Andrew
- Richardson Sylvia
- Richter Alex
- Roberts Irene
- Rogers T.
- Ross Robert MacKenzie
- Roughley Catherine
- Roy Noemi
- Sadeghi-Alavijeh Omid
- Saleem Moin
- Samani Nilesh
- Sanchis-Juan Alba
- Sargur Ravishankar
- Satchell Simon
- Savage K.
- Savic Sinisa
- Sawant K.
- Scelsi Laura
- Schulman Sol
- Scott R. H.
- Scully Marie
- Searle Claire
- Seeger Werner
- Sewell Carrock
- Seyres Denis
- Shapiro Susie
- Sharmardina Olga
- Shtoyerman Rakefet
- Sibson Keith
- Siddiq A.
- Side Lucy
- Sieghart A.
- Simeoni Ilenia
- Simpson Michael
- Sivapalaratnam Suthesh
- Skytte Anne-Bine
- Smith Katherine
- Smith Kenneth G. C.
- Smith S. C.
- Snape Katie
- Sosinsky A.
- Soubrier Florent
- Staines Simon
- Staples Emily
- Stark Hannah
- Stephens Jonathan
- Stirrups Kathleen
- Stock Sophie
- Stuckey A.
- Suntharalingam Jay
- Swietlik Emilia
- Syngelaki Argyro
- Tait R. Campbell
- Talks Kate
- Tan Rhea
- Tanguy M.
- Taylor Tavares A. L.
- Thaventhiran James
- Themistocleous Andreas
- Thomas E. R. A.
- Thomas Moira
- Thompson S. R.
- Thomson Kate
- Thorsell Malin
- Thrasher Adrian
- Thys Chantal
- Tischkowitz Marc
- Titterton Catherine
- Toh Cheng-Hock
- Toshner Mark
- Traylor Matthew
- Treacy Carmen
- Trembath Richard
- Tucci A.
- Tuna Salih
- Turek Wojciech
- Turro Ernest
- Vale Tom
- Van Geet Chris
- Van Zuydam Natalie
- Vazquez-Lopez Marta
- von Ziegenweidt Julie
- Waisfisz Quintin
- Walker Suellen
- Ware James
- Watkins Hugh
- Watt Christopher
- Webster Andrew
- Wei Wei
- Welch Steven
- Welland M. J.
- Wessels Julie
- Westbury Sarah
- Westwood John-Paul
- Wharton John
- Whitehorn Deborah
- Whitworth James
- Wilkins Martin R.
- Williams E.
- Williamson Catherine
- Witkowska K.
- Wong Edwin
- Wood Nicholas
- Wood S. M.
- Wood Yvette
- Woods Geoff
- Woodward Emma
- Wort Stephen
- Worth Austen
- Yates Katherine
- Yong Patrick
- Young Tim
- Yu Ping
- Yu-Wai-Man Patrick
- Zhang Jun
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 17/08/2022
- Field of study
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility
Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
- Author
- A Gordon Robertson
- Abdullah Kahraman
- Abel Gonzalez-Perez
- Adam A Margolin
- Adam Abeshouse
- Adam Grundhoff
- Adam J Struck
- Adam J Struck
- Adam J Wright
- Adam Lambert
- Adam P Butler
- Adam P Butler
- Adel El-Naggar
- Adnan M Nagrial
- Adrian Ally
- Adrian Baez-Ortega
- Adrian Thorogood
- Adriana Salcedo
- Adrienne M Flanagan
- Ake Borg
- Akihiro Fujimoto
- Akihiro Suzuki
- Akinyemi I Ojesina
- Alain Viari
- Alan J Robertson
- Alan P Hoyle
- Alan Thompson
- Alasdair Stenhouse
- Alastair M Thompson
- Aldo Scarpa
- Alessandro Pastore
- Alex Buchanan
- Alex Buchanan
- Alexander Claviez
- Alexander J Lazar
- Alexander Martinez-Fundichely
- Alfonso Muñoz
- Alfonso Valencia
- Aliaksei Z Holik
- Alice Meng
- Alicia L Bruzos
- Allison Creason
- Allison P Heath
- Alvin Wei Tian Ng
- Alvis Brazma
- Amaro Taylor-Weiner
- Amber L Johns
- Amie Radenbaugh
- Amit G Deshwar
- Ana Dueso-Barroso
- Ana Mijalkovic Mijalkovic-Lazic
- Ana Milovanovic
- Ana Milovanovic
- Andre Kahles
- Andrea Haake
- Andrea Holbrook
- Andrea L Richardson
- Andrea Mafficini
- Andrea Ruzzenente
- Andreas Behren
- Andreas Rosenwald
- Andreia V Pinho
- Andrew Berchuck
- Andrew D Cherniack
- Andrew J Dunford
- Andrew J Mungall
- Andrew J Spillane
- Andrew Menzies
- Andrew Menzies
- Andrew P Barbour
- Andrew Tutt
- Andrew V Biankin
- Andrey Korshunov
- Andrés Lanzós
- Andy Cafferkey
- Andy G Lynch
- Angela Chou
- Angela N Brooks
- Angela Tam
- Angelica Ochoa
- Angelika N Christ
- Angelo P Dei Tos
- Anieta M Sieuwerts
- Anil K Sood
- Anita Langerød
- Anja Füllgrabe
- Anke K Bergmann
- Ann-Marie Patch
- Anna deFazio
- Anna Ehinger
- Anna Fitzgerald
- Anne Hamilton
- Anne Vincent-Salomon
- Anne Y Warren
- Anne-Lise Børresen-Dale
- Annegien Broeks
- Anthony DiBiase
- Anthony J Gill
- Anthony Ng
- Anthony R Green
- Antonia L Pritchard
- Antonio Pea
- Antonios Koures
- Aparna Prasad
- Apurva M Hegde
- Aquila Fatima
- Arcadi Navarro
- Arie B Brinkman
- Arif O Harmanci
- Arindam Maitra
- Armando Lopez-Guillermo
- Arndt Borkhardt
- Arnoud Boot
- Asger Hobolth
- Ashley Williams
- Ashton A Connor
- Atul J Butte
- Aurélien Chateigner
- Austin J Hepperla
- Axel Aretz
- Aya Sasaki-Oku
- Ayellet V Segre
- B F Francis Ouellette
- Bailey Matthew H
- Barbara Hutter
- Barbara Hutter
- Barbara Kremeyer
- Bartha M Knoppers
- Beifang Niu
- Beifang Niu
- Beifang Niu
- Benedikt Brors
- Benita Kiat Tee Tan
- Benjamin J Raphael
- Benjamin P Berman
- Benjamin Raeder
- Bernardo Rodriguez-Martin
- Bernhard Radlwimmer
- Bernice H Wong
- Beth Karlan
- Bin Tean Teh
- Bin Zhu
- Birgit Burkhardt
- Bishoy M Faltas
- Bodil Bjerkehagen
- Bogdan Czerniak
- Boris Winterhoff
- Borislav C Rusev
- Bradly G Wouters
- Brandi N Davis-Dusenbery
- Brian Craft
- Brian D O'Connor
- Brian Patrick O'Neill
- Brice Aminou
- Calvin Wing Yiu Chan
- Cameron M Soulette
- Carl Herrmann
- Carl Morrison
- Carlo Gambacorti-Passerini
- Carlos Caldas
- Carlos D Bustamante
- Carlos López-Otín
- Carlota Rubio-Perez
- Carmen Gomez
- Carolien H M van Deurzen
- Carolyn M Hutter
- Carolyn M Hutter
- Carrie Cibulskis
- Caterina Vicentini
- Catherine A Shang
- Catherine D Moser
- Catherine J Kennedy
- Catrina C Fronick
- Chad J Creighton
- Chandra Sekhar Pedamallu
- Chang Li
- Charles David Imbusch
- Charles M Perou
- Charles Saller
- Charles Short
- Charlie E Massie
- Chawalit Pairojkul
- Chen Hong
- Chen Ye
- Cheng-Zhong Zhang
- Chin-Lee Wu
- Chip Stewart
- Chip Stewart
- Chip Stewart
- Choon Kiat Ong
- Chris Lawerenz
- Chris Mitchell
- Chris Sander
- Christian von Mering
- Christiane Buchholz
- Christina K Yung
- Christina K Yung
- Christina Yau
- Christine A Iacobuzio-Donahue
- Christine Chomienne
- Christine Desmedt
- Christine P'ng
- Christof von Kalle
- Christoph Borst
- Christoph Plass
- Christopher A Miller
- Christopher Benz
- Christopher J Scarlett
- Christopher J Yoon
- Christopher K Wong
- Christopher M Lalansingh
- Christopher M Lalansingh
- Christopher Ogden
- Christopher S Foster
- Christopher Umbricht
- Christopher W Toon
- Christos Sotiriou
- Cindy Bell
- Cinzia Cantù
- Ciyue Shen
- Claes Wadelius
- Clare Verrill
- Clarissa Gerhauser
- Claudia Calabrese
- Claudio Bassi
- Claudio Luchini
- Claudiu Farcas
- Clemency Jolly
- Colin A Purdie
- Colin A Semple
- Colin C Collins
- Colin S Cooper
- Conrad R Leonard
- Constance H Li
- Corbin D Jones
- Craig Shriver
- Cristina López
- Cyriac Kandoth
- Cyril Fisher
- D Neil Hayes
- Dai-Ying Wu
- Daiming Fan
- Daisuke Komura
- Dale W Garsed
- Daniel A Leongamornlert
- Daniel Baumhoer
- Daniel Hübschmann
- Daniel J Turner
- Daniel J Weisenberger
- Daniel M Berney
- Daniel Rosebrock
- Daniel S Brewer
- Daniela S Gerhard
- Danielle Pasternack
- Darell Bigner
- Dariush Etemadmoghadam
- Darlene Lee
- Darrin F Taylor
- Dave Larson
- David A Wheeler
- David A Wheeler
- David C Wedge
- David Craft
- David D L Bowtell
- David E Neal
- David Haan
- David Haussler
- David Haussler
- David Hedley
- David Huntsman
- David I Heiman
- David J Adams
- David J Van Den Berg
- David K Chang
- David K Miller
- David Khoo
- David Mutch
- David N Louis
- David Nicol
- David Ocana
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- David R Jones
- David Scott
- David T Bowen
- David T W Jones
- David Tamborero
- David Torrents
- David Torrents
- David Townend
- David Vicente
- Davide Antonello
- Declan Cahill
- Denis Larsimont
- Denis Yuen
- Denise Brooks
- Deniz Demircioğlu
- Dennis C Sgroi
- Dennis Karsch
- Dennis T Maglinte
- Dennis Wigle
- Derek W Wright
- Dianne E Chadwick
- Dido Lenze
- Dieter Kube
- Dieter Weichenhan
- Dilip D Giri
- Dimitri Livitz
- Dimitri Livitz
- Dimple Chakravarty
- Ding
- Dirk Schadendorf
- Dmitry A Gordenin
- Dominik Glodzik
- Don Chalmers
- Dong Guanlan
- Dongbing Liu
- Donghoon Lee
- Donghui Tan
- Donna M Muzny
- Dorthe Grabau
- Douglas A Levine
- Douglas F Easton
- Douglas Voet
- Duncan Beardsmore
- Dursi Lewis Jonathan
- Edward W Rowe
- Eigo Shimizu
- Ekta Khurana
- Elaine R Mardis
- Electron Kebebew
- Elena Piñeiro-Yáñez
- Elena Provenzano
- Elias Campo
- Elisabet Barrera
- Elisabetta Sereni
- Elizabeth A Musgrove
- Elizabeth L Appelbaum
- Elizabeth L Christie
- Elli Papaemmanuil
- Ellrott Kyle
- Emilie Lalonde
- Eoghan Harrington
- Eric Chuah
- Eric Green
- Eric Lander
- Eric Minwei Liu
- Eric Z Ma
- Eric Z Ma
- Erik Garrison
- Erik Larsson
- Erik Mayer
- Erik N Bergstrom
- Erin Curley
- Ermin Hodzic
- Erwin G Van Meir
- Esa Pitkänen
- Esther Rheinbay
- Esther Rheinbay
- Eun Pyo Hong
- Eunjung Alice Lee
- Eva G Alvarez
- Eva Hellstrom-Lindberg
- Ewan Birney
- F Germán Rodríguez-González
- Fabien C Lamaze
- Fabien Calvo
- Fabio C P Navarro
- Faiyaz Notta
- Fan Yang
- Fan Zhang
- Faraz Hach
- Faraz Hach
- Faridah Mbabaali
- Fatima Al-Shahrour
- Federico Abascal
- Fei-Fei Liu
- Felicity Newell
- Fenglin Liu
- Fernanda Amary
- Ferran Muiños
- Florian Markowetz
- Fouad Yousif
- Francesc Muyas
- Francesco Favero
- Francisco M De La Vega
- Francisco Sanchez-Vega
- Fraser R Duthie
- Fred Sweep
- Freddie C Hamdy
- Fruzsina Molnár-Gábor
- Fumie Hosoda
- G Petur Nielsen
- G Steven Bova
- Gad Getz
- Gad Getz
- Gad Getz
- Gaetan MacGrogan
- Gaetano Finocchiaro
- Gary D Bader
- Gavin Ha
- Gavin W Wilson
- Genta Nagae
- Geoff Macintyre
- George B Hanna
- George L Mihaiescu
- Georgia Escaramis
- Georgina V Long
- Gerd Nettekoven
- German M Demidov
- German Ott
- Gerrit K Hooijer
- Gerstein Mark B
- Gert G Van den Eynden
- Getz Gad
- Ghislaine Scelo
- Giada Bonizzato
- Giampaolo Tortora
- Gilles Romieu
- Gilles Thomas
- Giovanni Marchegiani
- Gisela Mir Arnau
- Giuseppe Malleo
- Gloria M Petersen
- Gordon B Mills
- Gordon B Mills
- Gordon Saksena
- Gordon Saksena
- Gordon Saksena
- Grace Tiao
- Grace Tiao
- Graham J Mann
- Grant Sanders
- Gu Kong
- Guanming Wu
- Guido Reifenberger
- Guido Sauter
- Guillaume Bourque
- Gulietta M Pupo
- Gun Ho Jang
- Gunes Gundem
- Gunnar Rätsch
- Gurnit Atwal
- Hailei Zhang
- Haiyan Irene Li
- Han Liang
- Hana Susak
- Hans Binder
- Hans Lehrach
- Hans-Jörg Warnatz
- Hardeep K Nahal-Bose
- Hark Kyun Kim
- HarshaVardhan Doddapaneni
- Hartmut Juhl
- Harvey Pass
- Hayley C Whitaker
- Hayley J Luxton
- Hazel Burke
- Heather K Schmidt
- Heather Thorne
- Hee Jin Lee
- Heidi J Sofia
- Heidi Sofia
- Helen Davies
- Helena Kilpinen
- Helene Kretzmer
- Heng Xiong
- Henk G Stunnenberg
- Henrik Hornshøj
- Henry Lee-Six
- Hideki Ohdan
- Hidenori Ojima
- Hidewaki Nakagawa
- Hikmat Al-Ahmadie
- Hilda A Pickett
- Hirofumi Rokutan
- Hirokazu Taniguchi
- Hiroki Yamaue
- Hiroko Tanaka
- Hiromi Nakamura
- Hiroshi Aikata
- Hiroto Katoh
- Hiroyuki Aburatani
- Hitoshi Katai
- Hitoshi Nakagama
- Hojabr Kakavand
- Holger Sültmann
- Holmfridur Hilmarsdottir
- Hong Su
- Hong Xue
- Hong Xue
- Hongtu Zhu
- Hongwei Zhang
- Hongxin Zhang
- Hsiao-Wei Chen
- Huanming Yang
- Hugh Barr
- Hui Shen
- Husen M Umer
- Huy Q Dinh
- Hyung-Lae Kim
- Hyung-Lae Kim
- Hyung-Yong Kim
- Hyunghwan Kim
- Ian J Davis
- Ian Welch
- Ignacio Vázquez-García
- Ignaty Leshchiner
- Ignaty Leshchiner
- Ignaty Leshchiner
- Iker Reyes-Salazar
- Ilinca Lungu
- Ilse Rooman
- Ilya Shmulevich
- Iman Sarrafi
- Iman Sarrafi
- Ina Felau
- Ioana Cutcutache
- Irene Papatheodorou
- Irinel Popescu
- Iris Pauporté
- Iris Selander
- Isabelle Treilleux
- Isidro Cortés-Ciriano
- Ivan Borozan
- Ivana Cataldo
- Ivica Letunic
- Ivica Letunic
- Ivo Buchhalter
- Ivo Buchhalter
- Ivo G Gut
- Ivo G Gut
- Ivon Harliwong
- Izar Villasante
- Iñigo Martincorena
- J Lynn Fink
- J Robert O'Neill
- J Todd Auman
- Jaclyn Smith
- Jacqueline Boultwood
- Jacqueline E Schein
- Jaegil Kim
- Jake June-Koo Lee
- Jakob Skou Pedersen
- Jakob Skou Pedersen
- James E Haber
- James G Kench
- James Gossage
- James S Wilmott
- Jan Komorowski
- Jan O Korbel
- Janae V Simons
- Jane E Brock
- Janet S Graham
- Janet S Rader
- Jared T Simpson
- Jared T Simpson
- Jason Huse
- Jaswinder S Samra
- Javier Bartolome
- Javier Bartolomé Rodriguez
- Javier Temes
- Jean C Zenklusen
- Jean Y Yang
- Jean-Rémi Trotta
- Jeffrey A Wintersinger
- Jeffrey Boyd
- Jeffrey E Gershenwald
- Jeffrey Marks
- Jeffrey Roach
- Jenna Eagles
- Jennifer L Jennings
- Jeong-Yeon Lee
- Jeremiah A Wala
- Jeremiah A Wala
- Jeremy Chien
- Jeremy Johns
- Jerome Myers
- Jesper Lagergren
- Jessica I Hoell
- Jessica K Miller
- Ji Wan Park
- Jia Liu
- Jian Wang
- Jianhong Hu
- Jianjiong Gao
- Jianmin Wu
- Jiashan Zhang
- Jiayin Wang
- Jiayin Wang
- Jieming Chen
- Jihoon Kim
- Jill Barnholtz-Sloan
- Jillian A Hung
- Jing Zhang
- Jingchun Zhu
- Joachim Weischenfeldt
- Joachim Weischenfeldt
- Joan Frigola
- Joana Carlevaro-Fita
- Jocelyne Jacquemier
- Joel S Parker
- Johan Staaf
- Johann S De Bono
- Johanna Bertl
- Johannes Werner
- Johannes Werner
- John A Demchok
- John A Foekens
- John Bartlett
- John Busanovich
- John D McPherson
- John F Thompson
- John Letaw
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- John N Weinstein
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- John V Pearson
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- Jon G Jonasson
- Jon W Teague
- Jon W Teague
- Jonas Demeulemeester
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- Jonathan Göke
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- Jonathan Hinton
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- Jonathan Spring
- Jonathan Warrell
- Jong K Kim
- Jongsun Jung
- Jongsun Jung
- Jongwhi H Hong
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- Josep L L Gelpi
- Joshua Armenia
- Joshua M Stuart
- Joshua M Stuart
- Joshy George
- José María Heredia-Genestar
- Joy C Jayaseelan
- Juergen Eils
- Juhee Lee
- Jules N A Kerssemakers
- Julia Markowski
- Julia Richter
- Julian M Hess
- Julian M Hess
- Julian M Hess
- Juliann Shih
- Julie Livingstone
- Julie M Wilson
- Jun Li
- Jun Yu
- Jung Kyoon Choi
- Junjun Zhang
- Junjun Zhang
- Juok Cho
- Juris Viksna
- Justin P Whalley
- Jyoti Nangalia
- Jörg Tost
- Jüri Reimand
- K Vijay Raghavan
- Kadir C Akdemir
- Kai Ye
- Kai Ye
- Kai Ye
- Kaixian Yu
- Kami Chiotti
- Kamna Ramakrishnan
- Kaoru Nakano
- Karen McCune
- Karen Mungall
- Karen Smith-McCune
- Karin A Oien
- Karin S Kassahn
- Karine Jegalian
- Karolina Czajka
- Karsten Rippe
- Katalin Karaszi
- Katarzyna O Sikora
- Katayoon Kasaian
- Katayoon Kasaian
- Katherine A Hoadley
- Kathleen H Burns
- Kathleen Marchal
- Kathryn Alsop
- Katia Nones
- Kazuaki Chayama
- Kazuhiro Maejima
- Kazuhiro Ohi
- Ke Yuan
- Keiran M Raine
- Keiran M Raine
- Keith A Boroevich
- Kelso Sean
- Ken Chen
- Ken Chen
- Ken Dutton-Regester
- Kenji Tatsuno
- Kenneth Aldape
- Keren Isaev
- Kerstin Haase
- Keun Soo Ahn
- Keunchil Park
- Kevin J Dawson
- Kevin Thai
- Kiejung Park
- Kin Chan
- Kiran Kumar
- Kirsten Kübler
- Kiyo Shimizu
- Kjong-Van Lehmann
- Klev Diamanti
- Koji Arihiro
- Koo Jeong Kang
- Kortine Kleinheinz
- Kortine Kleinheinz
- Kristian Cibulskis
- Kuan-Lin Huang
- Kui Wu
- Kunihito Gotoh
- Kwun M Fong
- Kyle Covington
- Kyle Covington
- Kyle Ellrott
- Kyle Ellrott
- Kyle Ellrott
- L Van't Veer
- Lara Jerman
- Lara Urban
- Lars Feuerbach
- Larsson Omberg
- Laura Planko
- Laurence B Lovat
- Laurent Arnould
- Lauri A Aaltonen
- Lawrence E Heisler
- Layla Oesper
- Lee E Timms
- Lei Song
- Leigh B Thorne
- Leng Han
- Leonidas Salichos
- Leslie Cope
- Leszek J Klimczak
- Levi Garraway
- Lewis Jonathan Dursi
- Lewis Jonathan Dursi
- Lewis R Roberts
- Li Ding
- Li Ding
- Li Ding
- Li Shantao
- Liang Wen-Wei
- Liangtao Zheng
- Lieven P C Verbeke
- Lihua Zou
- Liis Uusküla-Reimand
- Liliana Greger
- Liming Yang
- Lin Li
- Lina Sieverling
- Lina Wadi
- Lincoln D Stein
- Linda Mileshkin
- Linghua Wang
- LiRehan Akbani
- Lisa Lype
- Lisa Mirabello
- Lisle E Mose
- Liu Xi
- Liu Xi
- Lixing Yang
- Lora Lewis
- Lorenz H P Trümper
- Loretta M S Lau
- Lori Boice
- Loris Mularoni
- Lorraine A Chantrill
- Louis Letourneau
- Luc Dirix
- Luca Landoni
- Luca Malcovati
- Lucas Lochovsky
- Lucila Ohno-Machado
- Lucinda A Fulton
- Lucy Matthews
- Lucy Stebbings
- Lucy Stebbings
- Lucy Yates
- Ludmil B Alexandrov
- Ludmila Danilova
- Luisa Mantovani-Löffler
- Luke Marsden
- Maciej Wiznerowicz
- Malcolm Brock
- Malcolm J Moore
- Malene Juul
- Malik Alawi
- Mamoru Kato
- Manasa Ramakrishna
- Manaswi Gupta
- Manolis Kellis
- Manuel Prinz
- Mara Rosenberg
- Marat D Kazanov
- Marc D Perry
- Marc D Perry
- Marc J van de Vijver
- Marc Zapatka
- Marcel Kool
- Marcel Smid
- Marcin Imielinski
- Marco A Marra
- Marco Miotto
- Marcus Bosenberg
- Marek Cmero
- Maria Elisabeth Goebler
- Maria Keays
- Maria O'Donovan
- Maria Scardoni
- Maria Vittoria Davi
- Marie-Laure Yaspo
- Marina Pajic
- Mario Berrios
- Mario Cazzola
- Marius Rohde
- Mark A Rubin
- Mark B Gerstein
- Mark B Gerstein
- Mark H Wright
- Mark Lathrop
- Mark P Hamilton
- Mark Phillips
- Mark Pinese
- Mark Shackleton
- Markus B Schilhabel
- Markus Kreuz
- Markus Loeffler
- Markus Ringnér
- Marta Aymerich
- Marta Gut
- Marta Paczkowska
- Marta Tojo
- Martin Hansmann
- Martin L Ferguson
- Martin Peifer
- Mary J Goldman
- Masakazu Yamamoto
- Masaki Ueno
- Masashi Fujita
- Masashi Fukayama
- Matteo Fassan
- Matthew A Field
- Matthew A Reyna
- Matthew D Wilkerson
- Matthew Eldridge
- Matthew G Cordes
- Matthew G Soloway
- Matthew H Bailey
- Matthew H Bailey
- Matthew H Bailey
- Matthew J Anderson
- Matthew Meyerson
- Matthew R Huska
- Matthew Ringel
- Matthew W Fittall
- Matthias Bieg
- Matthias Bieg
- Matthias Schlesner
- Matthias Schlesner
- Mattia Bosio
- Maxime Tarabichi
- Maximillian G Marin
- Mayuko Furuta
- Mei Huang
- Melpomeni Kasapi
- Meyerson William U
- Mi Ni Huang
- Mia Nastic
- Michael A Hollingsworth
- Michael Birrer
- Michael C Heinold
- Michael C Heinold
- Michael C Quinn
- Michael C Wendl
- Michael C Wendl
- Michael D McLellan
- Michael D McLellan
- Michael D McLellan
- Michael Dunn
- Michael Fraser
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- Xinyue Li
- Xiuqing Zhang
- Xiuqing Zheng
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- Xuan Le
- Xuanping Zhang
- Xuemei Luo
- Xueqing Zou
- Yan Shi
- Yan Zhang
- Yang Wu
- Yang Yang
- Yann Joly
- Yanxun Xu
- Yao He
- Yasin Senbabaoglu
- Yassen Assenov
- Yasser Riazalhosseini
- Yasuhito Arai
- Yasushi Rino
- Yasushi Totoki
- Yeng Ang
- Yi Huang
- Yi Huang
- Yifei Men
- Yiling Lu
- Yilong Li
- Yingyan Yu
- Yiwen Chen
- Yogesh Kumar
- Yogesh Kumar
- Yoke-Eng Chiew
- Yong Hou
- Yong Zhou
- Yong-Jie Lu
- Yongzhan Nie
- Yosef E Maruvka
- Yosef E Maruvka
- Yoshiiku Kawakami
- Young Seok Ju
- Youngchoon Woo
- Youngil Koh
- Youngwook Kim
- Youyong Lu
- Yu Fan
- Yu Fan
- Yu Fan
- Yu-Jia Shiah
- Yuan Ji
- Yuan Yuan
- Yuichi Shiraishi
- Yulia Newton
- Yulia Rubanova
- Yumeng Wang
- Yupeng Cun
- Yussanne Ma
- Zachary Heins
- Zechen Chong
- Zechen Chong
- Zemin Zhang
- Zhaohong Chen
- Zhenggang Wu
- Zhenggang Wu
- Zhining Wang
- Zhongming Zhao
- Ziao Lin
- Zsofia Kote-Jarai
- Ólafur Andri Stefánsson
- Øystein Garred
- Publication venue
- Nature Communications
- Publication date
- 01/01/2020
- Field of study
Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts