6 research outputs found
Squamous Cell Carcinoma: PET/CT and PET/MRI of the Pretreatment and Post-Treatment Neck
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2019
- Field of study
The incidence of head and neck cancer continues to rise annually, most commonly squamous cell carcinoma (SCCa). Advances in imaging techniques have improved diagnostic accuracy with important ramifications for initial staging and post-treatment surveillance. FDG-PET/CT and, more recently, FDG-PET/MRI have revolutionized the staging and surveillance of head and neck SCCa. We detail the diagnostic role of FDG-PET/CT and FDG-PET/MRI of SCCa at the different head and neck subsites, highlighting their role in identifying the primary tumor extent, regional nodal metastases, and distant metastatic disease in the pretreatment and post-treatment setting, as well as implications for staging, treatment, and prognosis
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 InĂȘs
- 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 MĂ©lanie
- 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
- GrÀf 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 0.5â2% 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
Whole-genome sequencing of patients with rare diseases in a national health system
- Author
- Abbs Stephen
- Abulhoul Lara
- Adlard Julian
- Ahmed Munaza
- Aitman Timothy J.
- Aitman Timothy J.
- Alachkar Hana
- Allen Hana Lango
- Allen Hana Lango
- Allsup David J.
- Almeida-King Jeff
- Ancliff Philip
- Antrobus Richard
- Armstrong Ruth
- Arno Gavin
- Ashford Sofie
- Ashford Sofie
- Astle William J.
- Astle William J.
- Attwood Anthony
- Aurora Paul
- Babbs Christian
- Bacchelli Chiara
- Bakchoul Tamam
- Banka Siddharth
- Bariana Tadbir
- Barwell Julian
- Batista Joana
- Baxendale Helen E.
- Beales Phil L.
- Bennett David L.
- Bennett David L.
- Bentley David R.
- Bentley David R.
- Bierzynska Agnieszka
- Biss Tina
- Bitner-Glindzicz Maria A.K.
- Black Graeme C.
- Bleda Marta
- Blesneac Iulia
- Bockenhauer Detlef
- Bogaard Harm
- Bourne Christian J.
- Boyce Sara
- Bradley John R.
- Bradley John R.
- Bragin Eugene
- Breen Gerome
- Brennan Paul
- Brewer Carole
- Brod Naomi Clements
- Brown Matthew
- Browning Andrew C.
- Browning Michael J.
- Buchan Rachel J.
- Buckland Matthew S.
- Bueser Teofila
- Burn John
- Burns Siobhan O.
- Burren Oliver S.
- Burren Oliver S.
- Burrows Nigel
- Calleja Paul
- Calleja Paul
- Campbell Carolyn
- Carr-White Gerald
- Carss Keren
- Carss Keren
- Casey Ruth
- Castello Ignacio Medina
- Caulfield Mark J.
- Caulfield Mark J.
- Chambers Jenny
- Chambers John
- Chan Melanie M.Y.
- Cheah Calvin
- Cheng Floria
- Chinnery Patrick F.
- Chinnery Patrick F.
- Chitre Manali
- Christian Martin T.
- Church Colin
- Clayton-Smith Jill
- Cleary Maureen
- Coghlan Gerry
- Colby Elizabeth
- Cole Trevor R.P.
- Collins Janine
- Collins Peter W.
- Colombo Camilla
- Compton Cecilia J.
- Condliffe Robin
- Cook H. Terence
- Cook Stuart
- Cooper Nichola
- Corris Paul A A.
- Cunningham Fiona
- Curry Nicola S.
- Cutler Antony J.
- Daniels Matthew J.
- Dattani Mehul
- Daugherty Louise C.
- Davis John
- De Soyza Anthony
- Deevi Sri V.V.
- Deevi Sri V.V.
- Dent Timothy
- Deshpande Charu
- Dewhurst Eleanor F.
- Dixon Peter H.
- Dixon Peter H.
- Diz Carmen Bugarin
- Douzgou Sofia
- Downes Kate
- Downes Kate
- Drazyk Anna M.
- Drewe Elizabeth
- Duarte Daniel
- Dutt Tina
- Edgar J. David M.
- Edwards Karen
- Egner William
- Ekani Melanie N.
- Elliott Perry
- Erber Wendy N.
- Erwood Marie
- Estiu Maria C.
- Evans Dafydd Gareth
- Evans Gillian
- Everington Tamara
- Eyries MĂ©lanie
- Fassihi Hiva
- Favier Remi
- Findhammer Jack
- Fletcher Debra
- Flinter Frances A.
- Floto R. Andres
- Fowler Tom
- Fox James
- Frary Amy J.
- French Courtney E.
- Freson Kathleen
- Freson Kathleen
- Frontini Mattia
- Frontini Mattia
- Furnell Abigail
- Gale Daniel P.
- Gale Daniel P.
- Gall Henning
- Ganesan Vijeya
- Gattens Michael
- Geet Chris Van
- Geoghegan Claire
- Gerighty Terence S.A.
- Gharavi Ali G.
- Ghio Stefano
- Ghofrani Hossein Ardeschir
- Gibbs J. Simon R.
- Gibson Kate
- Gilmour Kimberly C.
- Girerd Barbara
- Gleadall Nicholas S.
- Goddard Sarah
- Goldstein David B.
- Gomez Keith
- Gordins Pavels
- Gosal David
- Graham Jodie
- Grassi Luigi
- Greene Daniel
- Greene Daniel
- Greenhalgh Lynn
- Greinacher Andreas
- Gresele Paolo
- Griffiths Philip
- Grigoriadou Sofia
- Grocock Russell J.
- Grozeva Detelina
- GrÀf Stefan
- GrÀf Stefan
- Gurnell Mark
- Hackett Scott
- Hadinnapola Charaka
- Hague Rosie
- Hague William M.
- Haimel Matthias
- Haimel Matthias
- Hall Matthew
- Hanson Helen L.
- Haque Eshika
- Harkness Kirsty
- Harper Andrew R.
- Harris Claire L L.
- Hart Daniel
- Hassan Ahamad
- Hayman Grant
- Henderson Alex
- Herwadkar Archana
- Hoffman Jonathan
- Holden Simon
- Horvath Rita
- Houlden Henry
- Houweling Arjan C C.
- Howard Luke S.
- Hu Fengyuan
- Hudson Gavin
- Hughes Joseph
- Huissoon Aarnoud P.
- Humbert Marc
- Humphray Sean
- Humphray Sean
- Hunter Sarah
- Hurles Matthew
- Irving Melita
- Izatt Louise
- James Roger
- James Roger
- Johnson Sally A.
- Jolles Stephen
- Jolley Jennifer
- Josifova Dragana
- Jurkute Neringa
- Karten Johannes
- Karten Tim
- Kasanicki Mary A.
- Kazkaz Hanadi
- Kazmi Rashid
- Kelleher Peter
- Kelly Anne M.
- Kelsall Wilf
- Kempster Carly
- Kiely David G.
- Kingston Nathalie
- Kingston Nathalie
- Klima Robert
- Koelling Nils
- Kostadima Myrto
- Kovacs Gabor
- Koziell Ania
- Koziell Ania
- Kreuzhuber Roman
- Kuijpers Taco W.
- Kumar Ajith
- Kumararatne Dinakantha
- Kurian Manju A.
- Laffan Michael A.
- Laffan Michael A.
- Lalloo Fiona
- Lambert Michele
- Lawrie Allan
- Layton D. Mark
- Lench Nick
- Lentaigne Claire
- Lester Tracy
- Levine Adam P.
- Levine Adam P.
- Linger Rachel
- Longhurst Hilary
- Lorenzo Lorena E.
- Louka Eleni
- Lyons Paul A.
- Machado Rajiv D.
- MacKenzie Ross Robert V.
- Madan Bella
- Maher Eamonn R.
- Maher Eamonn R.
- Maimaris Jesmeen
- Malka Samantha
- Mangles Sarah
- Mapeta Rutendo
- Mapeta Rutendo
- Marchbank Kevin J.
- Marks Stephen
- Markus Hugh S.
- Markus Hugh S.
- Marschall Hanns Ulrich
- Marshall Andrew
- Martin Jennifer
- Mathias Mary
- Matthews Emma
- Maxwell Heather
- McAlinden Paul
- McCarthy Mark I.
- McKinney Harriet
- McMahon Aoife
- Meacham Stuart
- Mead Adam J.
- Megy Karyn
- Megy Karyn
- Mehta Sarju G G.
- Michaelides Michel
- Millar Carolyn
- Mohammed Shehla N.
- Moledina Shahin
- Montani David
- Moore Anthony T.
- Morales Joannella
- Morales Joannella
- Morrell Nicholas W.
- Morrell Nicholas W.
- Mozere Monika
- Muir Keith W.
- Mumford Andrew D.
- Mumford Andrew D.
- Nemeth Andrea H.
- Newman William G.
- Newnham Michael
- Noorani Sadia
- Nurden Paquita
- Obaji Samya
- Odhams Chris
- Okoli Steven
- Olschewski Andrea
- Olschewski Horst
- Ong Kai Ren
- Oram S. Â Helen
- Ormondroyd Elizabeth
- Ormondroyd Elizabeth
- Ouwehand Willem H.
- Ouwehand Willem H.
- OâSullivan Jennifer
- Palles Claire
- Papadia Sofia
- Park Soo Mi
- Parry David
- Patel Smita
- Paterson Joan
- Peacock Andrew
- Pearce Simon H H.
- Peden John
- Peerlinck Kathelijne
- Penkett Christopher J.
- Penkett Christopher J.
- Pepke-Zaba Joanna
- Petersen Romina
- Pilkington Clarissa
- Poole Kenneth E.S.
- Prathalingam Radhika
- Psaila Bethan
- Pyle Angela
- Quinton Richard
- Rahman Shamima
- Rankin Stuart
- Rankin Stuart
- Rao Anupama
- Raymond F. Lucy
- Raymond F. Lucy
- Rayner-Matthews Paula J.
- Rees Christine
- Rendon Augusto
- Rendon Augusto
- Renton Tara
- Rhodes Christopher J.
- Rice Andrew S.C.
- Richardson Sylvia
- Richardson Sylvia
- Richter Alex
- Robert Leema
- Roberts Irene
- Roberts Irene
- Rogers Anthony
- Rose Sarah J.
- Ross-Russell Robert
- Roughley Catherine
- Roy Noemi B.A.
- Roy Noemi B. A
- Ruddy Deborah M.
- Sadeghi-Alavijeh Omid
- Saleem Moin A.
- Saleem Moin A.
- Samani Nilesh
- Samarghitean Crina
- Sanchis-Juan Alba
- Sanchis-Juan Alba
- Sargur Ravishankar B.
- Sarkany Robert N.
- Satchell Simon
- Savic Sinisa
- Sayer Genevieve
- Sayer John A.
- Scelsi Laura
- Schaefer Andrew M.
- Schulman Sol
- Scott Richard
- Scully Marie
- Searle Claire
- Seeger Werner
- Sen Arjune
- Sewell W. A.Carrock
- Seyres Denis
- Shah Neil
- Shamardina Olga
- Shamardina Olga
- Shapiro Susan E.
- Shaw Adam C.
- Short Patrick J.
- Sibson Keith
- Side Lucy
- Simeoni Ilenia
- Simpson Michael A A.
- Sims Matthew C.
- Sivapalaratnam Suthesh
- Smedley Damian
- Smith Katherine R.
- Smith Kenneth G.C.
- Smith Kenneth G.C.
- Snape Katie
- Soranzo Nicole
- Soubrier Florent
- Southgate Laura
- Spasic-Boskovic Olivera
- Staines Simon
- Staples Emily
- Stark Hannah
- Stark Hannah
- Stephens Jonathan
- Stephens Jonathan
- Steward Charles
- Stirrups Kathleen E.
- Stirrups Kathleen E.
- Stuckey Alex
- Suntharalingam Jay
- Swietlik Emilia M.
- Syrris Petros
- Tait R. Campbell
- Talks Kate
- Tan Rhea Y.Y.
- Tan Rhea Y.Y.
- Tate Katie
- Taylor Jenny C.
- Taylor John M.
- Thaventhiran James E.
- Themistocleous Andreas C.
- Themistocleous Andreas C.
- Thomas David
- Thomas Ellen
- Thomas Moira J.
- Thomas Patrick
- Thomson Kate
- Thrasher Adrian J.
- Thrasher Adrian J.
- Threadgold Glen
- Thys Chantal
- Thys Chantal
- Tilly Tobias
- Tischkowitz Marc
- Titterton Catherine
- Todd John A.
- Toh Cheng Hock
- Tolhuis Bas
- Tomlinson Ian P.
- Toshner Mark
- Traylor Matthew
- Treacy Carmen
- Treadaway Paul
- Trembath Richard
- Tuna Salih
- Tuna Salih
- Turek Wojciech
- Turro Ernest
- Turro Ernest
- Twiss Philip
- Vale Tom
- Vandekuilen Maarten
- Vandersteen Anthony M.
- Vazquez-Lopez Marta
- von Ziegenweidt Julie
- Vonk Noordegraaf Anton
- Wagner Annette
- Waisfisz Quinten
- Walker Neil
- Walker Neil
- Walker Suellen M.
- Walter Klaudia
- Ware James S.
- Watkins Hugh
- Watkins Hugh
- Watt Christopher
- Webster Andrew R.
- Webster Andrew R.
- Wedderburn Lucy
- Wei Wei
- Welch Steven B.
- Wessels Julie
- Westbury Sarah K.
- Westwood John Paul
- Wharton John
- Whitehorn Deborah
- Whitworth James
- Whitworth James
- Wilkie Andrew O. M
- Wilkins Martin R.
- Wilkins Martin R.
- Williamson Catherine
- Williamson Catherine
- Wilson Brian T.
- Wong Edwin K.S.
- Wood Nicholas
- Wood Yvette
- Woods Christopher Geoffrey
- Woodward Emma R R.
- Wort Stephen J.
- Worth Austen
- Wright Michael
- Yates Katherine
- Yong Patrick F.K.
- Young Timothy
- Yu Ping
- Yu-Wai-Man Patrick
- Zlamalova Eliska
- Zuydam Natalie van
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 02/07/2020
- Field of study
Most patients with rare diseases do not receive a molecular diagnosis and the aetiological variants and causative genes for more than half such disorders remain to be discovered1. Here we used whole-genome sequencing (WGS) in a national health system to streamline diagnosis and to discover unknown aetiological variants in the coding and non-coding regions of the genome. We generated WGS data for 13,037 participants, of whom 9,802 had a rare disease, and provided a genetic diagnosis to 1,138 of the 7,065 extensively phenotyped participants. We identified 95 Mendelian associations between genes and rare diseases, of which 11 have been discovered since 2015 and at least 79 are confirmed to be aetiological. By generating WGS data of UK Biobank participants2, we found that rare alleles can explain the presence of some individuals in the tails of a quantitative trait for red blood cells. Finally, we identified four novel non-coding variants that cause disease through the disruption of transcription of ARPC1B, GATA1, LRBA and MPL. Our study demonstrates a synergy by using WGS for diagnosis and aetiological discovery in routine healthcare
Publisher Correction: Whole-genome sequencing of a sporadic primary immunodeficiency cohort (Nature, (2020), 583, 7814, (90-95), 10.1038/s41586-020-2265-1)
- Author
- Abbs Stephen
- Adhya Zoe
- Adlard Julian
- Afzal Maryam
- Ahmed Irshad
- Ahmed Munaza
- Ahmed Saeed
- Aitman Timothy J.
- Alachkar Hana
- Alamelu Jayanthi
- Alikhan Raza
- Allen Carl E.
- Allen Louise
- Allsup David J.
- Alvi Arif
- Ambegaonkar Gautam
- Anantharachagan Ariharan
- Ancliff Philip
- Anderson Julie
- Antrobus Richard
- Armstrong Ruth
- Arno Gavin
- Arumugakani Gururaj
- Arya Rita
- Ashford Sofie
- Astle William J.
- Attwood Anthony
- Austin Steve
- Aydinok Yesim
- Ayub Waqar
- Babbs Christian
- Bacchelli Chiara
- Baglin Trevor
- Bakchoul Tamam
- Bariana Tadbir K.
- Barratt Jonathan
- Barwell Julian
- Baski John
- Bates Rachel W.
- Batista Joana
- Baxendale Helen E.
- Baxendale Helen E.
- Baynam Gareth
- Bennett David L.
- Bethune Claire
- Bhatnagar Neha
- Bibi Shahnaz
- Bierzynska Agnieszka
- Biss Tina
- Bitner-Glindzicz Maria A.K.
- Bleda Marta
- Blesneac Iulia
- Boardman Barbara
- Boddana Preetham
- Bogaard Harm J.
- Booth Claire
- Boschann Felix
- Boyce Sara
- Bradley John R.
- Brady Angela
- Breen Gerome
- Brennan Paul
- Brewer Carole
- Briley Annette
- Brod Naomi Clements
- Brown Matthew
- Brown Matthew
- Brown Richard
- Browning Michael J.
- Brownlie Mary
- Bryson Christine J.
- Buchan Rachel J.
- Buck Jackie
- Buckland Matthew S.
- Buckland Matthew S.
- Bueser Teofila
- Burns Siobhan O.
- Burns Siobhan O.
- Burren Oliver S.
- Burren Oliver S.
- Calleja Paul
- Carmichael Jenny
- Carr-White Gerald
- Carss Keren J.
- Casey Ruth
- Castello Ignacio Medina
- Chalmers Elizabeth
- Chambers Jenny
- Chambers John
- Chan Melanie M.Y.
- Chan Melissa V.
- Chandra Anita
- Chandra Anita
- Cheng Floria
- Chinn Ivan K.
- Chinnery Patrick F.
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- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 06/08/2020
- Field of study
An amendment to this paper has been published and can be accessed via a link at the top of the paper
Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis.
- Author
- Abrea Inna
- Adlard Julian
- Ahmad Ferhaan
- Ahmad Shazzra
- Ahmed Munaza
- Ahmed Sara
- Aitman Tim
- Alachkar Hana
- Allahua Melissa
- Allen Hana Lango
- Allsup David
- Almeida-King Jeff
- Almeida-Peters Sisama
- Aman Jurjan
- Amouyel Philippe
- Ancliff Philip
- Anderson Audrey
- Andrews Mary
- Antrobus Richard
- Archer Stephen L
- Argula Rahul
- Arkon Abby
- Armstrong Ruth
- Arno Gavin
- Arora Amit
- Ashford Sofie
- Astle William
- Aston Valerie
- Attwood Anthony
- Austin Eric D
- Ayesh Waleed
- Babbs Chris
- Badesch David
- Bakchoul Tamam
- Bakshi Sahil
- Bariana Tadbir
- Barnett Christopher
- Barve Mukta
- Barwell Julian
- Batai Ken
- Beckmann Joy
- Bennett David
- Bentley David
- Benza Raymond
- Bhatt Nitin
- Bierzynska Agnieszka
- Bindu John
- Birru Hellina
- Biss Tina
- Blake Randy
- Bleda Marta
- Boekwig Deedre
- Bogaard Harm
- Bogaard Harm J
- Bourne Christian
- Boyce Sara
- Bradley John
- Brady Daniela
- Breen Gerome
- Brennan Paul
- Brewer Carole
- Broach Debra
- Brod Naomi Clements
- Brody Linnea
- Brown Matthew
- Browning Michael
- Bruno Jackie
- Buchan Rachel
- Buckland Matthew
- Bueser Teofila
- Burger Charles D
- Burns Siobhan
- Burren Oliver
- Calleja Paul
- Carr-White Gerald
- Carss Keren
- Casanova Nancy
- Casey Ruth
- Caskey Elizabeth
- Caulfield Mark
- Cebola Ines
- Chakinala Murali
- Chambers Jennifer
- Chambers John
- Cheng Floria
- Chinnery Patrick F
- Christian Martin
- Church Colin
- Coghlan Gerry
- Coghlan John G
- Colby Elizabeth
- Cole Trevor
- Collins Janine
- Collins Peter
- Colombo Camilla
- Condliffe Robin
- Cook Stuart
- Cook Terry
- Cooper Nichola
- Cope Molly
- Cordell Shannon
- Correa Priscilla
- Corris Paul
- Corris Paul A
- Crisp-Hihn Abigail
- Curry Nicola
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- Favier Remi
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- Fortin Terry
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- French Courtney
- Freson Kathleen
- Frontini Mattia
- Frost Adaani
- Gale Daniel
- Gall Henning
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- Germain Marine
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- Ghofrani Hossein-Ardeschir
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- Graf Stefan
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- Greinacher Andreas
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- Hassan Ahamad
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- Hawkes Nicholas
- Hayman Grant
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- Houweling Arjan C
- Howard Luke
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- Hudson Gavin
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- Huissoon Aarnoud
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- Iem Thoeun
- Igenoza Tosin
- Ingledue Rebecca
- Ivy Dunbar
- Izatt Louise
- Jackson Esperanza
- James Roger
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- Klinger James
- Knight Jo
- Kostadima Myrto
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- Koziell Ania
- Kreuzhuber Roman
- Kuijpers Taco
- Kumar Ajith
- Kumararatne Dinakantha
- Kurian Manju
- Laffan Michael
- Lahm Tim
- Lalloo Fiona
- Lambert Michele
- Larimore Daniel
- Laudes Matthias
- Lawrie Allan
- Layton Mark
- Lee Jennifer
- Lemma Merte
- Lentaigne Claire
- Levine Adam
- Lewis Karlise
- Light Allison
- Linger Rachel
- Longhurst Hilary
- Louka Eleni
- Lovato Ellen
- Lutz Katie
- MacDonald Catherine
- Machado Rajiv D
- Madan Bella
- Maher Eamonn
- Maimaris Jesmeen
- Malur Anagha
- Mangles Sarah
- Mapeta Rutendo
- Marchbank Kevin
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- Meacham Stuart
- Mead Adam
- Megy Karyn
- Mehta Sarju
- Mendibles Lillian
- Michaelides Michel
- Millar Carolyn
- Miller-Reed Kathleen
- Moledina Shahin
- Montani David
- Moore Tony
- Morrell Nicholas
- Morrell Nicholas W
- Mozere Monika
- Muir Keith
- Mumford Andrew
- Nathan Steven D
- Newnham Michael
- Nichols William C
- Noordegraaf Anton Vonk
- Norwood Tracy
- O'Sullivan Jennifer
- Obaji Samya
- Okoli Steven
- Olanipekun Lekan
- Olschewski Andrea
- Olschewski Horst
- Ong Kai Ren
- Ormiston Mark
- Ormondroyd Elizabeth
- Oudiz Ronald J
- Ouwehand Willem
- Ouwehand Willem H
- Paciotti Gina
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- Palmisciano Amy
- Papadia Sofia
- Park Soo-Mi
- Parry David
- Paterson Joan
- Pauciulo Michael W
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- Peerlinck Kathelijne
- Peichel Gretchen
- Penkett Christopher
- Pepke-Zaba Joanna
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- Pisarcik Jessica
- Prokopenko Inga
- Pyle Angela
- Rankin Stuart
- Rao Anupama
- Raymond F Lucy
- Rayner-Matthews Paula
- Rees Christine
- Rehman Zia
- Rendon Augusto
- Renton Tara
- Reponen Auvo
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- Rice Andrew
- Richardson Sylvia
- Richter Alex
- Roads Tammy
- Robbins Ivan
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- Roden Dan M
- Rohwer Kristal
- Rosenzweig Erika B
- Ross Robert MacKenzie
- Ross Robert V MacKenzie
- Roughley Catherine
- Rowley Courtney
- Roy Noemi
- Sadeghi-Alavijeh Omid
- Saleem Moin
- Samani Nilesh
- Sanchis-Juan Alba
- Santiago Joseph
- Sargur Ravishankar
- Satchell Simon
- Savic Sinisa
- Saydain Ghulam
- Scelsi Laura
- Schiltz Kimberly
- Schilz Robert
- Schulman Sol
- Scovel Page
- Scully Marie
- Searle Claire
- Seeger Werner
- Sewell Carrock
- Seyres Denis
- Shaffer Christian M
- Shapiro Susie
- Sharmardina Olga
- Shtoyerman Rakefet
- Sibson Keith
- Side Lucy
- Simeoni Ilenia
- Simms Robert W
- Simon Marc
- Simpson Michael
- Singleton Donna
- Sitbon Olivier
- Sivapalaratnam Suthesh
- Skytte Anne-Bine
- Smith Katherine
- Smith Kenneth GC
- Snape Katie
- Soubrier Florent
- Southgate Laura
- Spears Jill
- Staines Simon
- Staples Emily
- Stark Hannah
- Stephens Jonathan
- Stirrups Kathleen
- Stock Sophie
- Stratoberdha Melissa
- Stratton Eric
- Suntharalingam Jay
- Swietlik Emilia
- Swietlik Emilia M
- Szuberla Sylwia
- Tait R Campbell
- Talks Kate
- Tan Rhea
- Tang Haiyang
- Tavlarides Andrea
- Tchourbanov Alexander Y
- Thaventhiran James
- Themistocleous Andreas
- Thenappan Thenappan
- Theuer Alison
- Thomas Moira
- Thomson Kate
- Thrasher Adrian
- Thys Chantal
- Tischkowitz Marc
- Titterton Catherine
- Toh Cheng-Hock
- Tomer David
- Torres Fernando
- Toshner Mark
- Toshner Mark R
- Traylor Matthew
- Treacy Carmen
- Treacy Carmen M
- Tregouet David-Alexandre
- Trembath Richard
- Trembath Richard C
- Tuna Salih
- Turek Wojciech
- Turk Erin
- Turro Ernest
- Ulrich Anna
- Urban Tracy
- Vale Tom
- Van Geet Chris
- Van Zuydam Natalie
- Vang Brenda
- Vazquez-Lopez Marta
- Visnaw Karen
- Von Ziegenweidt Julie
- Waisfisz Quinten
- Waisfisz Quintin
- Walker Suellen
- Walsworth Anna K
- Walter Robert E
- Warden Ashley
- Ware James
- Watkins Hugh
- Watt Christopher
- Webster Andrew
- Wei Wei
- Welch Steven
- Wessels Julie
- Westbury Sarah
- Westwood John-Paul
- Wharton John
- White R James
- Whitehorn Deborah
- Whitman Renesa
- Whitworth James
- Wilkins Martin R
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- Williamson Catherine
- Wilson Opal
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- Wood Nicholas
- Wood Yvette
- Woods Geoff
- Woodward Emma
- Wort Stephen
- Wort Stephen J
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- Yates Katherine
- Yong Patrick
- Young Tim
- Yu Ping
- Yu-Wai-Man Patrick
- Yung Delphine
- Ziemak Caitlin
- Publication venue
- Lancet Respir Med
- Publication date
- 26/09/2018
- Field of study
BACKGROUND: Rare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes. METHODS: We did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension. These GWAS used data from four international case-control studies across 11â744 individuals with European ancestry (including 2085 patients). One GWAS used genotypes from 5895 whole-genome sequences and the other GWAS used genotyping array data from an additional 5849 individuals. Cross-validation of loci reaching genome-wide significance was sought by meta-analysis. Conditional analysis corrected for the most significant variants at each locus was used to resolve signals for multiple associations. We functionally annotated associated variants and tested associations with duration of survival. All-cause mortality was the primary endpoint in survival analyses. FINDINGS: A locus near SOX17 (rs10103692, odds ratio 1·80 [95% CI 1·55-2·08], p=5·13âĂâ10-15) and a second locus in HLA-DPA1 and HLA-DPB1 (collectively referred to as HLA-DPA1/DPB1 here; rs2856830, 1·56 [1·42-1·71], p=7·65âĂâ10-20) within the class II MHC region were associated with pulmonary arterial hypertension. The SOX17 locus had two independent signals associated with pulmonary arterial hypertension (rs13266183, 1·36 [1·25-1·48], p=1·69âĂâ10-12; and rs10103692). Functional and epigenomic data indicate that the risk variants near SOX17 alter gene regulation via an enhancer active in endothelial cells. Pulmonary arterial hypertension risk variants determined haplotype-specific enhancer activity, and CRISPR-mediated inhibition of the enhancer reduced SOX17 expression. The HLA-DPA1/DPB1 rs2856830 genotype was strongly associated with survival. Median survival from diagnosis in patients with pulmonary arterial hypertension with the C/C homozygous genotype was double (13·50 years [95% CI 12·07 to >13·50]) that of those with the T/T genotype (6·97 years [6·02-8·05]), despite similar baseline disease severity. INTERPRETATION: This is the first study to report that common genetic variation at loci in an enhancer near SOX17 and in HLA-DPA1/DPB1 is associated with pulmonary arterial hypertension. Impairment of SOX17 function might be more common in pulmonary arterial hypertension than suggested by rare mutations in SOX17. Further studies are needed to confirm the association between HLA typing or rs2856830 genotyping and survival, and to determine whether HLA typing or rs2856830 genotyping improves risk stratification in clinical practice or trials. FUNDING: UK NIHR, BHF, UK MRC, Dinosaur Trust, NIH/NHLBI, ERS, EMBO, Wellcome Trust, EU, AHA, ACClinPharm, Netherlands CVRI, Dutch Heart Foundation, Dutch Federation of UMC, Netherlands OHRD and RNAS, German DFG, German BMBF, APH Paris, INSERM, UniversitĂ© Paris-Sud, and French ANR
Search for intermediate-mass black hole binaries in the third observing run of Advanced LIGO and Advanced Virgo
- Author
- Abbott Rich
- Abbott Thomas D.
- Acernese Fausto
- Ackley Kendall
- Adams Carl
- Adhikari Naresh
- Adhikari Rana X.
- Adya Vaishali B.
- Affeldt Christoph
- Agarwal Deepali
- Agathos Michalis
- Agatsuma Kazuhiro
- Aggarwal Nancy
- Aguiar Odylio D.
- Aiello Lorenzo
- Ain Anirban
- Ajith P.
- Akutsu Tomotada
- Albanesi Simone
- Allocca Annalisa
- Altin Paul A.
- Amato Alex
- Anand Chandana
- Anand Shreya
- Ananyeva Alena
- Anderson Stuart B.
- Anderson Warren G.
- Ando Masaki
- Andrade Tomas
- Andres Nicolas
- AndriÄ Tomislav
- Angelova Svetoslava V.
- Ansoldi Stefano
- Antelis J.M.
- Antier Sarah
- Appert Stephen
- Arai Koji
- Arai Koya
- Arai Yuya
- Araki Sakae
- Araya Akito
- Araya Melody C.
- Areeda Joseph S.
- Arellano Fabian E. Peña
- Aritomi Naoki
- Arnaud Nicolas
- Aronson Scott M.
- Arun Kg G.
- ArĂšne Marc
- Asada Hideki
- Asali Yasmeen
- Ashton Gregory
- Aso Yoichi
- Assiduo Maria
- Aston Stuart M.
- Astone Pia
- Aubin Florian
- Austin Corey
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- Badaracco Francesca
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- Wipf Christopher C.
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- Wofford Jared K.
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- Wu David S.
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- Wysocki Daniel M.
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- Xu W-R.
- Yamada Tomohiro
- Yamamoto Hiro
- Yamamoto Kazuhiro
- Yamamoto Kohei
- Yamamoto Takahiro
- Yamashita Kanta
- Yamazaki Ryo
- Yang Fengwei W.
- Yang Le
- Yang Yang
- Yang Yi
- Yang Ziyan
- Yap M.J.
- Yeeles David W.
- Yelikar Anjali B.
- Ying Make
- Yokogawa Kazuya
- Yokoyama J.
- Yokozawa Takaaki
- Yoo Jooheon
- Yoshioka Toshiya
- Yu Hang
- Yu Haocun
- Yuzurihara Hirotaka
- ZadroĆŒny Adam
- Zanolin Michele
- Zeidler Simon
- Zelenova Tatiana
- Zendri J.-P.
- Zevin Michael
- Zhan Mingsheng
- Zhang Hong
- Zhang Jue
- Zhang Liyuan
- Zhang Teng
- Zhang Yanqi
- Zhao Chunnong
- Zhao Guoying
- Zhao Yue
- Zhao Yuhang
- Zhou Ruinan
- Zhou Zifan
- Zhu Xingjiang J.
- Zhu Z.-H.
- Zimmerman Aaron B.
- Zlochower Y.
- Zucker Michael E.
- Zweizig John
- Publication venue
- 'EDP Sciences'
- Publication date
- 01/01/2022
- Field of study
International audienceIntermediate-mass black holes (IMBHs) span the approximate mass range 100â105âMâ, between black holes (BHs) that formed by stellar collapse and the supermassive BHs at the centers of galaxies. Mergers of IMBH binaries are the most energetic gravitational-wave sources accessible by the terrestrial detector network. Searches of the first two observing runs of Advanced LIGO and Advanced Virgo did not yield any significant IMBH binary signals. In the third observing run (O3), the increased network sensitivity enabled the detection of GW190521, a signal consistent with a binary merger of mass âŒ150âMâ providing direct evidence of IMBH formation. Here, we report on a dedicated search of O3 data for further IMBH binary mergers, combining both modeled (matched filter) and model-independent search methods. We find some marginal candidates, but none are sufficiently significant to indicate detection of further IMBH mergers. We quantify the sensitivity of the individual search methods and of the combined search using a suite of IMBH binary signals obtained via numerical relativity, including the effects of spins misaligned with the binary orbital axis, and present the resulting upper limits on astrophysical merger rates. Our most stringent limit is for equal mass and aligned spin BH binary of total mass 200âMâ and effective aligned spin 0.8 at 0.056 Gpcâ3 yrâ1 (90% confidence), a factor of 3.5 more constraining than previous LIGO-Virgo limits. We also update the estimated rate of mergers similar to GW190521 to 0.08 Gpcâ3 yrâ1.Key words: gravitational waves / stars: black holes / black hole physicsCorresponding author: W. Del Pozzo, e-mail: [email protected]â Deceased, August 2020