50 research outputs found
Policing Persons with Mental Illness in Georgia: Elucidating Perceptions of the Mental Health System
- Author
- Publication venue
- ScholarWorks @ Georgia State University
- Publication date
- 06/01/2012
- Field of study
The criminal justice and mental health systems increasingly overlap as persons with mental illness (PMI) are disproportionately present throughout components of the criminal justice system, a concern to mental health and criminal justice professionals alike. In response, various initiatives (aimed across components of the criminal justice system) have been developed and implemented as a means of combating this overrepresentation. The following research will focus on one specialized police-based initiative, the Crisis Intervention Team (CIT), which aims to train police how to recognize mental illness, de-escalate persons in crisis, and to seek treatment-based alternatives to arrest, when appropriate (Schwarzfeld, Reuland, & Plotkin, 2008). Alternatives to arrest consist of various community-based mental health services such as public hospitals (some of which are designated as emergency receiving facilities, or ERFs) or private clinics. While the components of CIT training likely influence officers in unique ways, research has yet to empirically examine how CIT influences police perception, behavior or the incidence of referrals to mental health treatment. As an initial step, this research assessed the attitudes police have regarding the hospital and mental health system within their district. Specifically, this research provides a basic understanding of how police regard their local hospitals and mental health facilities that are posited as available alternatives to arrest, and help identify the role CIT plays in shaping these attitudes. This study found almost no significant difference in the attitudes CIT-trained officers had towards district ERF and the local mental health system as compared to non-CIT officers. Only in one of the six departments studied was there a significant difference between the attitudes of CIT-officers and non-CIT officers; with the non-CIT officers actually having more positive attitudes about their local mental health system than CIT-officers. The six departments studied had nearly similar attitudes of their mental health resources, which would barely be considered passing on a standard grading scale. While officers in this study do not have very positive attitudes towards the ERF they use to transport PMI or their districts’ mental health system, these attitudes may in fact be more positive than many police departments without any specialized approach or initiative. The significance and policy implications of these attitudes are discussed at length, as these findings speak to the need for increased attention by both the mental health and criminal justice systems. Recommendations for future research, including expanding this study to rural departments or agencies with no connection to CIT, are also outlined
A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.
- Author
- Adonina Tardón
- AF Kantor
- AL Price
- Alan Schned
- Alessandra Allione
- Alfredo Carrato
- Alison Johnson
- Amanda Black
- Amy Hutchinson
- Anne E Kiltie
- Anne Tjonneland
- Ashley Godfrey
- Bogdan Czerniak
- Borje Ljungberg
- BW Zanke
- C Murta-Nascimento
- Carlotta Sacerdote
- Carmen Navarro
- Colin P Dinney
- Consol Serra
- CP Strassburg
- CP Strassburg
- CP Strassburg
- D Clayton
- D Crowther-Swanepoel
- DA Bell
- Dalsu Baris
- David J Hunter
- David T Bishop
- David Van Den Berg
- Debra T Silverman
- Demetrius Albanes
- DF Easton
- Dimitrios Trichopoulos
- DW Hein
- Elio Riboli
- Eric J Jacobs
- Eugen Gurzau
- Federico Canzian
- Francisco X Real
- Francoise Clavel-Chapelon
- Fulvio Ricceri
- Gabriel Valdivia
- Gerald Andriole
- Geraldine Cancel-Tassin
- Giuseppe Matullo
- GM Lower Jr.
- GM Petersen
- H Bas Bueno-de-Mesquita
- Holger Dietrich
- Hushan Yang
- Immaculata De Vivo
- IP Tomlinson
- J Alfred Witjes
- J Richter
- Jack A Taylor
- Jan G Hengstler
- Jarmo Virtamo
- JE Wigginton
- JH Park
- Jian-Min Yuan
- JK Pritchard
- Jonine D Figueroa
- Jose I Mayordomo
- Josep Lloreta
- Joseph F Fraumeni
- José I Sanz-Velez
- K Iida
- K Yu
- KA Frazer
- Kari Stefansson
- Katja K Aben
- KD Tsakiri
- Kevin B Jacobs
- KK Aben
- Klaus Golka
- Kvetoslava Koppova
- L Giuliani
- L Sun
- LA Kiemeney
- LA Kiemeney
- Lambertus A Kiemeney
- Laurie Burdett
- Ludmila Prokunina-Olsson
- M García-Closas
- M Malumbres
- M Yeager
- M Yeager
- Malcolm C Pike
- Manolis Kogevinas
- Manuel Sanchez
- Manuela Gago-Dominguez
- Margaret A Knowles
- Margaret R Karagas
- Maria Teresa Landi
- Mariana C Stern
- Mark P Purdue
- Mark T W Teo
- María D García-Prats
- Meng Chen
- Meredith Yeager
- Michael Thun
- Michelle A T Hildebrandt
- ML Freedman
- Molly Schwenn
- Monica McGrath
- Montserrat Garcia-Closas
- MT Landi
- MY Armanios
- N Patterson
- N Rothman
- Naomi E Allen
- Nathaniel Rothman
- Neil Caporaso
- Nilanjan Chatterjee
- Nuria Malats
- Olivier Cussenot
- P Fearnhead
- P Fearnhead
- Paolo Vineis
- Patrick Sulem
- Paul Brennan
- Peter Rudnai
- PI de Bakker
- RA Eeles
- Rajiv Kumar
- Reina García-Closas
- Remco R Makkinje
- Robert Grubb
- Robert N Hoover
- RT Calado
- RT Calado
- S Shete
- Salvatore Panico
- SG Conticello
- Silvia Polidoro
- Silvia Selinski
- Simone Benhamou
- Simonetta Guarrera
- Sita H Vermeulen
- SN Stacey
- Sophia C E Bolick
- Soren Besenbacher
- Stefano Porru
- Stephanie J Weinstein
- Stephen J Chanock
- Susan M Gapstur
- T Rafnar
- Thorunn Rafnar
- Tony Fletcher
- Victoria K Cortessis
- W Ryan Diver
- William Wheeler
- X Wu
- Xifeng Wu
- Y Ando
- Yi-Ping Fu
- Zhaoming Wang
- Zongli Xu
- Publication venue
- Nature Research
- Publication date
- 01/01/2010
- Field of study
We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis
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.
- 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.
- Aguero D.
- Ahmad N.
- Ahmadi S.
- Ahmed A.
- Ahmed C.
- Akeroyd L.
- Akhtar M. N.
- Akinkugbe O.
- Aksentijevich 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.
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- Almalki F.
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- Zyndorf M.
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2022
- Field of study
Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease
Genetic mechanisms of critical illness in COVID-19.
- Author
- A A Roger Thompson
- A Abraheem
- A Agasou
- A Ahmed
- A Ali
- A Allan
- A Altabaibeh
- A Alvaro
- A Aspinwall
- A Ayers
- A Bamford
- A Barron
- A Bashyal
- A Bellini
- A Bociek
- A Botello
- A Bowes
- A Brady
- A Brayne
- A Brown
- A Brown
- A Butler
- A Campbell
- A Carter
- A Collins
- A Cowley
- A Cowton
- A Cowton
- A Cox
- A Crew
- A Dance
- A Daniel
- A Daniels
- A Dela Rosa
- A Drummond
- A Durie
- A E Heron
- A Easthope
- A Easthope
- A Evans
- A Fofano
- A Gales
- A Ganesan
- A Gardner
- A Garg
- A Gherman
- A Gordon
- A Gratrix
- A Gulati
- A Gupta
- A Haigh
- A Haldeos
- A Harrison
- A Harvey
- A Hayes
- A Higham
- A Higham
- A Hilldrith
- A Holden
- A Hormis
- A Hutcheon
- A Javaid
- A Joseph
- A Kaliappan
- A Katary
- A Kay
- A Kayani
- A Kent
- A Kirkby
- A Knight
- A Kubisz-Pudelko
- A Kuravi
- A Lewis
- A Loveridge
- A Lyle
- A Mayer
- A McAlpine
- A McCarthy
- A McGregor
- A McGregor
- A Meikle
- A Mitchell
- A Mitra
- A Morris
- A Morrison
- A Naranjo
- A Nicholson
- A Nicholson
- A Nilsson
- A Noakes
- A Patel
- A Pickard
- A Poole
- A Price
- A Puxty
- A Quinn
- A Quinn
- A Raithatha
- A Rattray
- A Reddy
- A Reed
- A Reyes
- A Rose
- A Rose
- A Rostron
- A Roy
- A Roynon-Reed
- A S Raj
- A Salberg
- A Sanderson
- A Serrano-Ruiz
- A Solesbury
- A Sukha
- A Swain
- A Tariq
- A Thomas
- A Thomas
- A Todd
- A Tomas
- A Tridente
- A Tucci
- A Turnbull
- A Uriel
- A Ustianowski
- A Vochin
- A Vuylsteke
- A Waite
- A Walden
- A Whileman
- A Wilkinson
- A Williams
- A Williams
- A Wilson
- A Zak
- A Zaki
- Achille Iolascon
- Adam Auton
- Adam Brown
- Agnese Verzuri
- Agostino Ognibene
- Agostino Riva
- Ailsa Golightly
- Alan Maclean
- Alessandra
- Alessandra Stella
- Alessandra Vergori
- Alessia Giorli
- Alexander J Mentzer
- Alice Donati
- Alison M Meynert
- Alistair Nichol
- Ana da Silva Filipe
- Andrea Antinori
- Andrea Cossarizza
- Andrea Ganna
- Andrea Tommasi
- Andrew Rambaut
- Andrew Stenhouse
- Andy Law
- Anjali J Shastri
- Anna Canaccini
- Anna Maria Pinto
- Annarita Giliberti
- Annemarie B Docherty
- Antonella D'Arminio Monforte
- Antonia Ying Wai Ho
- Antonio Di Biagio
- Antony Symons
- Arianna Emiliozzi
- Arianna Gabrieli
- Audrey Coutts
- B Anwar
- B Attwood
- B Baines
- B Blackledge
- B Borislavova
- B Chandler
- B Charles
- B Creagh-Brown
- B David
- B Deacon
- B Deacon
- B Digby
- B Faulkner
- B Fuller
- B Gumbrill
- B Gurung
- B Hadebe
- B Hairsine
- B Hopkins
- B Johnston
- B Lenagh
- B Masunda
- B Ogg
- B Patel
- B Player
- B Purewal
- B Scholefield
- B Shelley
- B Sloan
- B Thomas
- B Wadams
- B Welsh
- B Wilkinson
- B Winter-Goodwin
- B Yates
- Baillie J Kenneth
- Barbara Rossetti
- Beale Rupert
- Beatrice Alex
- Benjamin Bach
- Bretherick Andrew D
- Bruno Frediani
- C Adams
- C Ahmed
- C Almaden-Boyle
- C Ashbrook-Raby
- C Basikolo
- C Battle
- C Beazley
- C Beith
- C Borra
- C Brandwood
- C Brantwood
- C Burnett
- C Castro Delgado
- C Clark
- C Clulow
- C Collins
- C Cruz
- C Davis
- C Demetriou
- C Dennis
- C Dexter
- C Downes
- C Dunmore
- C Eastgate
- C Eckbad
- C Finch
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- 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
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- C Pothecary
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- 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
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- C Whitton
- C Whyte
- C Wrey Brown
- Cameron J Fairfield
- Carmelo Piscopo
- Carmen Marciano
- Caroline Abernathy
- Carrol Gamble
- Caterina Lo Rizzo
- Catherine A Shaw
- Catherine H Weldon
- Caulfield Mark
- Ceilia Boz
- Cesira Nencioni
- Chelsea Ye
- Chiara Fallerini
- Chiara Gabbi
- Chiara Spertilli
- Chloe Donohue
- Chris Ponting
- Christoper A Green
- Cinthia E Jannes
- Clare Jackson
- Clohisey Sara
- Cristina Mussini
- D Antcliffe
- D Bakthavatsalam
- D Banach
- D Baptista
- D Bell
- D Branney
- D Brealey
- D Brealey
- D Butcher
- D Butcher
- D Childs
- D Clarke
- D Collier
- D Collier
- D Cristiano
- D Dawson
- D Donaldson
- D Duffin
- D Fottrell-Gould
- D Golden
- D Griffin
- D Hamilton
- D Hawcutt
- D Hope
- D Horner
- D Kallon
- D Kaye
- D Kelly
- D Loader
- D Lomas
- D Martin
- D McGlynn
- D McLaughlanv
- D Melia
- D Menzies
- D Mullan
- D Pogson
- D Potla
- D Potoczna
- D Purohit
- D Raynard
- D Salutous
- D Salutous
- D Scaletta
- D Shaw
- D Skinner
- D Smyth
- D Strachan
- D Tetla
- D Thornton
- D Trodd
- D Vedage
- D Walker
- D Warren
- D Williams
- D Wood
- D Wright
- Daniela Francisci
- Daniella Coker
- Danilo Tacconi
- David A van Heel
- David Bennet
- David L Robertson
- David Stuart
- Dawn Law
- Debby Bogaert
- Derek Murphy
- Domenico A Coviello
- E Abaleke
- E Allan
- E Anastasescu
- E Andrews
- E Apetri
- E B Jude
- E Beech
- E Beranova
- E Bevan
- E Black
- E Brinkworth
- E Collins
- E Combes
- E Davies
- E Dobson
- E Dooks
- E Fisher
- E Gendall
- E Goff
- E Goodwin
- E Gordon
- E Heeney
- E Horsley
- E Hughes
- E Johnson
- E Knights
- E Lee
- E London
- E Maccacari
- E Massey
- E McKenna
- E Meadows
- E Moncur
- E Morino
- E Mwaura
- E Peasgood
- E Perkins
- E Radford
- E Raith
- E Raith
- E Salciute
- E Smith
- E Smithson
- E Stoddard
- E Stones
- E Thomas
- E Tilney
- E Timlick
- E Treus Gude
- E Virgilio
- E Watson
- E Wilby
- Edoardo Conticini
- Egle Saviciute
- Elena Bargagli
- Elena Desanctis
- Elisa Benetti
- Elisa Frullanti
- Elisabetta Menatti
- Elisabetta Schiaroli
- Ellie Mcmaster
- Emma C Thomson
- Emmanuelle Marques
- Enrico Martinelli
- Esther Duncan
- Esther Merlini
- Ewen M Harrison
- F Anderson
- F Auld
- F Bibi
- F Davies
- F Farquhar
- F Fisher
- F Hurford
- F Kibutu
- F McNeela
- F Moore
- F Nasir
- F Trim
- F Wakinshaw
- F Williams
- Fabio Lena
- Fawkes Angie
- Federico Anedda
- Federico Franchi
- Ferdinando Giannattasio
- Filip Taneski
- Filippo Aucella
- Filippo Biscarini
- Floriana Valentino
- Fourman Max Head
- Francesca Andretta
- Francesca Fava
- Francesca Gatti
- Francesca Mari
- Francesca Montagnani
- Francesco Castelli
- Francesco Raimondi
- Furniss James
- G Andrew
- G Arbane
- G Bell
- G Bercades
- G Croston
- G Debreceni
- G Durrant
- G Hambrook
- G Hobden
- G Houston
- G Hughes
- G Jones
- G Lubimbi
- G Maloney
- G Martir
- G Millen
- G Mills
- G O'Connor
- G Padden
- G Randell
- G Sadera
- G Seddon
- G Sera Howe
- G Sloane
- G Subramanian
- G Tsinaslanidis
- G Turner
- G Watson
- G Wray
- Gabriella Coiro
- Gabriella Doddato
- Gail Carson
- Gardar Sveinbjornsson
- Gary Leeming
- Genni Spargi
- Georgios Pollakis
- Giacomo Zanelli
- Gian Piero Caldarelli
- Giancarlo Bosio
- Giuseppe Fiorentino
- Giuseppe Merla
- Gountouna Elvina
- Graham S Cooke
- Griffiths Fiona
- Grimes Graeme
- H Bancroft
- H Bates
- H Belfield
- H Blackman
- H Blakemore
- H Brooke
- H Button
- H Coles
- H Curgenven
- H Filipe
- H Fox
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- H Houlden
- H Jeffrey
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- H Langton
- H McGuinness
- H Meghari
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- H Prady
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- H Rangarajan
- H Rehman
- H Reschreiter
- H Riley
- H Sainsbury
- H Savill
- H Sturgeon
- H T-Michael
- H Tench
- H Tiveran
- H Turner
- H Whittle
- H Willis
- H Wood
- Haley Chris
- Hanning Mal
- Harrison David
- Hayley Hardwick
- Hayward Caroline
- Helen Szoor-McElhinney
- Hinds Charles
- Ho Antonia
- Horby Peter
- I Ali Mohamed Ali
- I Balagosa
- I Birkinshaw
- I Burn
- I Chadbourn
- I D Clement
- I Edmond
- I Frost
- I Hass
- I Hussain
- I Lancoma-Malcolm
- I Leadbitter
- I Nagra
- I Otahal
- I Otahal
- I Turner-Bone
- I Welters
- I White
- I Wynter
- Ilaria Meloni
- Immacolata Andolfo
- Isabella Zanella
- J Allan
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- J Camsooksai
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- J Caterson
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- J Cockerill-Taylor
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- J Egan
- J Fernandez Roman
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- Sandro Panese
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- Sara McDonald
- Sarah Law
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- Stefania Mantovani
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- Stefano Rusconi
- Stella Aslibekyan
- Stephanie Roberts
- Stephen R Knight
- Summers Charlotte
- Susanna Croci
- Susanna Guerrini
- T Anderson
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- T Smith
- T Smith
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- 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
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- V Linnett
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- V Page
- V Parris
- V Parris
- V Pristopan
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- V Rivers
- V Sarathy
- V Thomas
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- 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
New genetic loci link adipose and insulin biology to body fat distribution.
- Author
- Aalto Ville
- Aasarød Knut
- Abecasis Goncalo R
- Abecasis Gonçalo
- Absher Devin
- Adair Linda S
- Adam Martin
- Adeyemo Adebowale
- Ahlqvist Emma
- Ahmadi Kourosh R
- Ahola Aila
- Ainali Chrysanthi
- Akylbekova Ermeg
- Ala-Korpela Mika
- Alavere Helen
- Albagha Omar M E
- Albrecht Eva
- Alen Markku
- Alexander Myriam
- Alhenc-Gelas François
- Alizadeh Behrooz Z
- Allison Matthew A
- Alonso Nerea
- Altshuler David
- Ambite Jose Luis
- Amin Najaf
- Amouyel Philippe
- An Ping
- Anderson Carl A
- Anderson Denise
- Anderson Garnet
- Andrews Jeanette S
- Antonella Mulas
- Antti Jula
- Aragaki Aaron K
- Arking Dan E
- Arnold Alice
- Arnold Alice M
- Arora Pankaj
- Arscott Gillian M
- Artigas Maria Soler
- Arveiler Dominique
- Asiki Gershim
- Aspelund Thor
- Assimes Themistocles L
- Atalay Mustafa
- Atkinson Elizabeth J
- Aulchenko Yurii
- Avery Christy
- Bain Stephen C
- Bakker Stephan J L
- Balcells Susana
- Balkau Beverley
- Ballantyne Christie M
- Balmforth Anthony J
- Bandinelli Stefania
- Barbalic Maja
- Barrett Amy
- Barroso Ines
- Barroso Inês
- Basart Hanneke
- Basart Hanneke V
- Bataille Veronique
- Baumert Jens
- Beckmann Jacques S
- Beekman Marian
- Been Latonya F
- Beilby John
- Beilby John P
- Bell Jordana T
- Bellis Claire
- Bennett Amanda J
- Bennett Franklyn
- Berenson Gerald S
- Bergman Richard N
- Bergmann Sven
- Berndt Sonja I
- Berne Christian
- Bidulescu Aurelian
- Bielak Lawrence F
- Bierut Laura J
- Biffar Reiner
- Bis Joshua C
- Blackburn Hannah
- Blangero John
- Blankenberg Stefan S
- Blüher Matthias
- Boban Mladen
- Bochud Murielle
- Boehm Bernhard O
- Boehnke Michael
- Boerwinkle Eric
- Boezen H Marike
- Bolton Jennifer L
- Bolton Judith A Hoffman
- Bonnet Fabrice
- Bonnycastle Lori L
- Boomsma Dorret I
- Borecki Ingrid
- Boright Andrew P
- Borja Judith B
- Bornstein Stefan R
- Boston Jonathan
- Bots Michiel L
- Bouatia-Naji Nabila
- Bouchard Claude
- Bovet Pascal
- Boyd Heather A
- Bragg-Gresham Jennifer L
- Brambilla Paolo
- Brand Eva
- Brand Stefan-Martin
- Brandi Maria Luisa
- Braund Peter S
- Brennan Eoin P
- Brismar Kerstin
- Brody Jennifer
- Broekmans Frank J
- Broer Linda
- Brown Matthew A
- Brown Morris J
- Brown-Gentry Kristin
- Bruinenberg Marcel
- Buchkovich Martin L
- Buckley Brendan M
- Buil Alfonso
- Bull Shelley B
- Burgdorf Christof
- Buring Julie E
- Burnett Mary S
- Burnier Michel
- Burri Andrea
- Burton Paul R
- Bush William S
- Busonero Fabio
- Buxbaum Sarah G
- Buyske Steve
- Buzkova Petra
- Byrne Enda M
- Böger Carsten A
- Böhringer Stefan
- Böttcher Yvonne
- Cambien Francois
- Campbell Harry
- Campbell Susan
- Carba Delia B
- Carlson Chris
- Carlson Olga D
- Carty Cara
- Casas Juan P
- Caspersen Ida H
- Castano-Betancourt Martha
- Cauchi Stéphane
- Cauley Jane A
- Caulfield Mark
- Cavalieri Margherita
- Cazier Jean-Baptiste
- Center Jacqueline R
- Cesana Giancarlo
- Chakravarti Aravinda
- Chambers John
- Chandak Giriraj R
- Chang Hsing-Yi
- Chang Yen-Pei C
- Chanock Stephen J
- Charchar Fadi J
- Chasman Dan
- Chaturvedi Nish
- Chen Constance
- Chen Han
- Chen Ida
- Chen Jin
- Chen Ming-Huei
- Chen Wei
- Chen Yii-Der Ida
- Cheng Iona
- Cheng Sulin
- Chines Peter S
- Cho Yoon Shin
- Choi Murim
- Chouraki Vincent
- Christiansen Claus
- Chu Audrey Y
- Cimponeriu Dan
- Ciullo Marina
- Clark Graeme R
- Clarke Robert
- Claudi-Boehm Simone
- Coassin Stefan
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- Cooper Jackie A
- Cooper Matthew N
- Cooper Richard S
- Coresh Josef
- Cornelis Marilyn C
- Corre Tanguy
- Corsi Anna Maria
- Couper David
- Cousminer Diana L
- Coviello Andrea D
- Cox David
- Crawford Dana
- Crisponi Laura
- Croteau-Chonka Damien C
- Cucca Francesco
- Cummings Steven R
- Cupples Adrienne L
- Cupples L Adrienne
- Curhan Gary
- d'Adamo Pio
- Dahgam Santosh
- Dailiana Zoe
- Danesh John
- Danoy Patrick
- Dastani Zari
- Davies Gail
- Daw E Warwick
- Day Felix R
- Day Ian N M
- de Andrade Mariza
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- Dedoussis George
- Dedoussis George V
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- Deelen Joris
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- Delgado Graciela
- Deloukas Panagiotis
- Deloukas Panos
- Demerath Ellen W
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- Denniff Matthew
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- Dermitzakis Emmanouil T
- Deshmukh Harshal
- Deshmukh Harshal A
- Devuyst Olivier
- di Meglio Paola
- Diemert Patrick
- Dimas Antigone S
- Dimitriou Maria
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- Dreisbach Albert W
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- Duggan David
- Dumitrescu Logan
- Duncan Bruce B
- Duncan Emma L
- Dupuis Josee
- Dupuis Josée
- Durbin Richard
- Durda Peter
- Döring Angela
- Dörr Marcus
- Eastell Richard
- Easton Douglas F
- Ebrahim Shah
- Econs Michael J
- Edkins Sarah
- Egan Josephine
- Ehret Georg
- Eiriksdottir Gudny
- Eisman John A
- Eklund Niina
- El Mokhtari NourEddine
- Elks Cathy E
- Ellinghaus David
- Elliott Paul
- Elosua Roberto
- Emilsson Valur
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- Epstein Stephen E
- Erbel Raimund
- Erdmann Jeanette
- Erdos Michael R
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- Eriksson Johan
- Eriksson Niclas
- Eriksson Per
- Ernst Florian
- Esko Tonu
- Esko Tõnu
- Esko Tönu
- Estrada Karol
- Eury Elodie
- Evangelou Evangelos
- Evans Alun
- Evans David M
- Eyheramendy Susana
- Eyjolfsson Gudmundur Ingi
- Fagerholm Emma
- Falhammar Henrik
- Fall Tove
- Farrall Martin
- Fauser Bart C J M
- Fava Cristiano
- Feenstra Bjarke
- Fehrmann Rudolf
- Feitosa Mary
- Feranil Alan B
- Ferrannini Ele
- Ferrario Marco M
- Ferreira Teresa
- Ferreli Liana
- Ferrières Jean
- Ferrucci Luigi
- Fischer Krista
- Florez Jose C
- Folkersen Lasse
- Folsom Aaron R
- Fontanillas Pierre
- Ford Ian
- Fornage Myriam
- Foroud Tatiana
- Forouhi Nita G
- Forrester Terrence
- Forsblom Carol
- Foster Meredith C
- Fowke Jay
- Fowkes F Gerald R
- Fowkes Gerard R
- Fox Caroline S
- Fox Ervin R
- Franceschini Nora
- Franco Oscar H
- Franco-Cereceda Anders
- Franke Andre
- Franke Lude
- Franks Paul W
- Frants Rune
- Fraser Ross M
- Frayling Timothy M
- Freedman Barry I
- Freimer Nelson B
- Freitag Daniel F
- Friedrich Nele
- Froguel Philippe
- Frost Morten
- Fuchsberger Christian
- Galan Pilar
- Ganesh Santhi K
- Ganna Andrea
- Gansevoort Ron T
- Gao Xiaoyi
- Garcia Melissa
- Garcia-Giralt Natàlia
- Garnaas Maija
- Gasparini Paolo
- Gauguier Dominique
- Gaunt Tom R
- Gautvik Kaare M
- Geller Frank
- Gharavi Ali G
- Giedraitis Vilmantas
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- Williams Frances M K
- Williams Rasheeda
- Williams Winfred W
- Willner Dana
- Wilsgaard Tom
- Wilson James F
- Wilson James G
- Wilson Sarah
- Wilson Scott G
- Winkler Thomas
- Witteman Jacqueline C
- Witteman Jacqueline C M
- Wojczynski Mary K
- Wolffenbuttel Bruce H R
- Wong Andrew
- Wong Tien Y
- Woo Jean
- Wood Andrew R
- Wood Andy
- Workalemahu Tsegaselassie
- Wright Alan F
- Wu Chunyuan
- Wu Joseph M W
- Wu Ying
- Würtz Peter
- Xiao Su-Mei
- Yajnik Chittaranjan S
- Yang Jian
- Yang Qiong
- Yang Tsun-Po
- Yao Jie
- Yengo Loïc
- Yerges-Armstrong Laura M
- Young Alicia
- Young Elizabeth H
- Young J H
- Young Lauren
- Yuan Xin
- Zaboli Ghazal
- Zalloua Pierre A
- Zarrabeitia María T
- Zelenika Diana
- Zemunik Tatijana
- Zerbini Gianpaolo
- Zgaga Lina
- Zhai Guangju
- Zhang Feng
- Zhang Qunyuan
- Zhang Weihua
- Zhao Jing Hua
- Zhao Wei
- Zheng Hou-Feng
- Zheng Wei
- Zhou Yanhua
- Zhu Haidong
- Zhu Kun
- Zhu Xiaofeng
- Zhuang Wei V
- Zhuang Wei Vivian
- Ziegler Andreas
- Zillikens M Carola
- Zimmermann Martina E
- Zitting Paavo
- Zondervan Krina T
- Zukowska-Szczechowska Ewa
- Zygmunt Marek
- Ärnlöv Johan
- Österholm Anne-May
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2015
- Field of study
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms
Avian β-defensin variation in bottlenecked populations : the Seychelles warbler and other congeners
- Author
- A Aguilar
- A Dijk van
- A Ferrer-admetlla
- AK Turner
- B Hansson
- B Hansson
- B Murrell
- B Murrell
- BP Lazzaro
- BT Chow
- C Oosterhout van
- C Oosterhout van
- C Oosterhout Van
- C Pertoldi
- C Vila
- CE Grueber
- CE Grueber
- Cock van Oosterhout
- D Garrigan
- D Ma
- D Yang
- Danielle Gilroy
- David S. Richardson
- DJ Lynn
- DJ Wright
- DJ Wright
- DL Richardson
- DM Tompkins
- DM Tompkins
- DR Ardia
- DS Richardson
- DS Richardson
- DS Richardson
- DS Richardson
- DS Richardson
- DS Richardson
- EJ Hollox
- ELB Barrett
- F Tajima
- H Ellegren
- H Jensen
- H Sugiarto
- HC Miller
- IG Jamieson
- J Crommenacker van de
- J Felsenstein
- J Klein
- J Komdeur
- J Komdeur
- J Marchini
- J Radwan
- J Tu
- JA Eimes
- Jan Komdeur
- JL Bollmer
- JM Meredith
- JT Hogg
- JT Sutton
- JT Sutton
- K Acevedo-Whitehouse
- K Schulze-Hagen
- K Tamura
- K Tamura
- KJM Jeffery
- KT Ramasamy
- L Brouwer
- L Brouwer
- L Zhu
- LA Meyers
- LG Spurgin
- LG Spurgin
- LG Spurgin
- M Alcaide
- M Anisimova
- M Basu
- M Brooke
- M Kimura
- M Nei
- M Nei
- M Raymond
- M Stephens
- M Stephens
- M Vögeli
- MDL Brooke
- ME Selsted
- MJ Fitzpatrick
- N Saitou
- O Hellgren
- O Hellgren
- O Hellgren
- O Hellgren
- OH Frankel
- P Kaiser
- P Librado
- PC Doherty
- PW Hedrick
- PW Hedrick
- R Frankham
- R Higgs
- R Safford
- REW Hancock
- S Bensch
- S Mukherjee
- S Sommer
- SB Piertney
- SC Knowles
- SJ O’Brien
- SL Pimm
- T Ohta
- TA Hall
- TA Schlenke
- TH Jukes
- W Delport
- WK Potts
- WSW Wong
- Y Xiao
- Y-X Fu
- Y-X Fu
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2016
- Field of study
β-defensins are important components of the vertebrate innate immune system responsible for encoding a variety of anti-microbial peptides. Pathogen-mediated selection is thought to act on immune genes and potentially maintain allelic variation in the face of genetic drift. The Seychelles warbler, Acrocephalus sechellensis, is an endemic passerine that underwent a recent bottleneck in its last remaining population, resulting in a considerable reduction in genome-wide variation. We genotyped avian β-defensin (AvBD) genes in contemporary (2000–2008) and museum samples (1876–1940) of the Seychelles warbler to investigate whether immunogenetic variation was lost through this bottleneck, and examined AvBD variation across four other Acrocephalus species with varying demographic histories. No variation was detected at four of the six AvBD loci screened in the post-bottleneck population of Seychelles warbler, but two silent nucleotide polymorphisms were identified at AvBD8 and one potentially functional amino-acid variation was observed at AvBD11. Variation in the Seychelles warbler was significantly lower than in the mainland migratory congeneric species investigated, but it similar to that found in other bottlenecked species. In addition, screening AvBD7 in 15 museum specimens of Seychelles warblers sampled prior to the bottleneck (1877–1905) revealed that this locus possessed two alleles previously, compared to the single allele in the contemporary population. Overall, the results show that little AvBD variation remains in the Seychelles warbler, probably as a result of having low AvBD diversity historically rather than the loss of variation due to drift associated with past demographic history. Given the limited pathogen fauna, this lack of variation at the AvBD loci may currently not pose a problem for this isolate population of Seychelles warblers, but it may be detrimental to the species’ long-term survival if new pathogens reach the population in the future
Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
- Author
- Abbas M.
- Abdul Rasheed A.
- Abdul A.
- Abdul-Kadir R.
- Abdusamad K.
- Abernethy K.
- Aboelela H.
- Abouzaid M.
- Abraham M.
- Abraham T.
- Abrams J.
- Abu H.
- Abu-Arafeh A.
- Acton C.
- Adam F.
- Adam M.
- Adams C.
- Adams C.
- Adams D.
- Adams L.
- Addo A.
- Adedeji O.
- Adegoke K.
- Adewunmi E.
- Adeyemo T.
- Agbeko R.
- Aggarwal S.
- Ahmad S.
- Ahmed A.
- Ahmed I.
- Ahmed M.
- Ahmed R.
- Ahmed R.
- Ainsworth M.
- Ajmi A.
- Akili S.
- Al Aaraj A.
- Al Balushi A.
- Al-Asadi A.
- Al-Khalil M.
- Al-Ramadhani B.
- Al-Saadi Z.
- Al-Shahi Salman R.
- Al-Sheklly B.
- Albert P.
- Alegria A.
- Alexander A.
- Alexander P.
- Alhabsha O.
- Ali M.
- Ali M.
- Aliberti E.
- Alin J.
- Aliyuda F.
- Alkhudhayri A.
- Allan N.
- Allanson A.
- Allen E.
- Allen L.
- Alshaer I.
- Altaf S.
- Amezaga M.
- Amin A.
- Amit B.
- Anand A.
- Anantapatnaikuni S.
- Anderson L.
- Anderson M.
- Anderson M.
- Anderson N.
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- Anguvaa L.
- Aniruddhan K.
- Antonina Z.
- Araujo M.
- Archer A.
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- Armistead J.
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- Arora D.
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- Wong C.
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- Wood J.
- Wood L.
- Woodfield R.
- Woodford E.
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- Woodhead L.
- Woodward Z.
- Woodward Z.
- Wooldridge G.
- Woollen L.
- Wootton D.
- Worton S.
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- Yaqoob N.
- Yasmin S.
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- Yates T.
- Yelnoorkar F.
- Yelnoorkar F.
- Yeoh A.
- Younes Ibrahim A.
- Young L.
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- Publication venue
- Springer Science and Business Media LLC
- Publication date
- 31/01/2024
- Field of study
Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome
Whole-genome sequencing reveals host factors underlying critical COVID-19
- Author
- Abd Elghafar M.S.
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- 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
Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
- Author
- Abbas M.
- Abdul Rasheed A.
- Abdul A.
- Abdul-Kadir R.
- Abdusamad K.
- Abernethy K.
- Aboelela H.
- Abouzaid M.
- Abraham M.
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- Acton C.
- Adam F.
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- Adeyemo T.
- Agbeko R.
- Aggarwal S.
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- Ainsworth M.
- Ajmi A.
- Akili S.
- Al Aaraj A.
- Al Balushi A.
- Al-Asadi A.
- Al-Khalil M.
- Al-Ramadhani B.
- Al-Saadi Z.
- Al-Shahi Salman R.
- Al-Sheklly B.
- Albert P.
- Alegria A.
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- Central Coordinating Office (for the RECOVERY Collaborative Group)
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- Dalgleish H.
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- Darbyshire Janet
- Darnell S.
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- Dasgin J.
- Data Monitoring Committee of the RECOVERY Collaborative Group
- Daunt A.
- Dave V.
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- Dhillon R.
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- Dimitri P.
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- Durrington H.
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- Fairbairn I.
- Fairclough A.
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- Health records (for the RECOVERY Collaborative Group)
- Hector G.
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- Jaime F.
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- Jameson J.
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- Jarvis C.
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- Jeffery Katie
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- Jenkins P.
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- Jerry D.
- Jimenez Gil A.
- Johal S.
- John A.
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- Johnstone E.
- Jones A.
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- Jordache R.
- Jose S.
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- Joseph R.
- Josiah B.
- Ju Wen Kwek A.
- Judge P.
- Juszczak Edmund
- Kailey A.
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- Local Clinical Centre staff (for the RECOVERY Collaborative Group)
- Lock S.
- Locke T.
- Lockett T.
- Lodhia K.
- Lofthouse M.
- Logan M.
- Logue C. A.
- Lokanathan S.
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- Mahaveer A.
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- Maheswaran A.
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- Majekdunmi T.
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- Manso K.
- Mansour M.
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- Maria del Rocio F.
- Mariano V.
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- May P.
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- Metryka A.
- Mew L.
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- Montgomery Alan
- Moon A.
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- Morrow A.
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- Mtuwa S.
- Muazzam A.
- Mudawi D.
- Mulcahy M.
- Mulligan S.
- Mumford Andrew
- Munavvar Mohammed
- Munt S.
- Murphy S.
- Murray C.
- Murray D.
- Murray I.
- Murray K.
- Murray L.
- Murthy M.
- Mutch C.
- Muzengi N.
- Mwaura E.
- Nafei M.
- Nagarajan T.
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- Nandani A.
- Nandwani T.
- Nasa S.
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- Neal A.
- Nelson B.
- Nelson S.
- Nethercott D.
- Newby D.
- Newman T.
- Newport R.
- Ng S.
- Ngumo A.
- Nicholas N.
- Nicholas P.
- Nickson I.
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- Nightingale T.
- Nilsson A.
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- Nirmalan M.
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- Oliver A.
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- Oxlade R.
- O’Brien R.
- O’Callaghan C.
- O’Connor G.
- O’Donovan C.
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- O’Riordan D.
- O’Sullivan E.
- Padden G.
- Page I.
- Page S.
- Pagett K.
- Pajak S.
- Pakou G.
- Palacios A.
- Palfrey H.
- Pandya T.
- Panes A.
- Pantin C.
- Parambil V.
- Parashar S.
- Parekh A.
- Parekh D.
- Parker B.
- Parker J.
- Parker S.
- Parkinson A.
- Passby L.
- Passey S.
- Patachako J.
- Patel M.
- Patel P.
- Patel S.
- Patience A.
- Patten S.
- Patterson C.
- Patterson L.
- Pauls L.
- Paulus S.
- Payne B.
- Payne E.
- Payne R.
- Peacock L.
- Pearce J.
- Pearson K.
- Peasley A.
- Peggie H.
- Pelham C.
- Penman C.
- Penman J.
- Penman R.
- Percival R.
- Perez E.
- Periyasamy L.
- Perry A.
- Perry M.
- Pessoa-Amorim Guilherme
- Peters C.
- Peterson A.
- Peto Leon
- Petrova B.
- Pezard-Snell M.
- Phelan P.
- Philbin J.
- Phillips N.
- PI M.
- Pick S.
- Pickard J.
- Pickering G.
- Piercy C.
- Pinches H.
- Pine K.
- Pinjala M.
- Pitchford M.
- Pleass R.
- Plowright M.
- Plumptre C.
- Pomery F.
- Poole L.
- Porter D.
- Porter L.
- Potter A.
- Potts J.
- Poustie V.
- Power N.
- Poyner E.
- Pradhan V.
- Prady H.
- Prasath S.
- Pratt A.
- Pratt S.
- Preiss D.
- Prest C.
- Price A.
- Price C.
- Price D.
- Price K.
- Price L.
- Price V.
- Price-Eland R.
- Priest A.
- Prince C.
- Pringle S.
- Pristopan V.
- Priyash V.
- Prudon Benjamin
- Pugh L.
- Purdue C.
- Purdy R.
- Pursell M.
- Purvis S.
- Putensen D.
- Pyart E.
- Quek E.
- Quigley J.
- Quindoyos J.
- Quinn T.
- Rabinowicz S.
- Rafique J.
- Rahman M.
- Rai S.
- Raithatha A.
- Rajasri A.
- Ramanan A.
- Ramasamy M.
- Ramchandani A.
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- Ramsay J.
- Ramshaw A.
- Rana G.
- Rand J.
- Rank H.
- Rankhelawon R.
- Rasheed A.
- Ratcliffe S.
- Raw J.
- Razvi Z.
- RECOVERY Collaborative Group
- Redknap I.
- Redman N.
- Rees A.
- Rees M.
- Rees S.
- Rehman Z.
- Reilly M.
- Reith C.
- Renshaw S.
- Rey S.
- Reynard C.
- Reynolds H.
- Rhodes J.
- Rice E.
- Rice M.
- Rice N.
- Richardson E.
- Richardson N.
- Rigby L.
- Riley M.
- Riley P.
- Ripley D.
- Rishton C.
- Riste M.
- Ritchings A.
- Rivera Ortega P.
- Robbins E.
- Roberts V.
- Robertson C.
- Robertson J.
- Robertson N.
- Robinson J.
- Robinson L.
- Robinson S.
- Robson S.
- Roderick M.
- Rodger A.
- Rodgers A.
- Rodgers N.
- Rodgers P.
- Roehr C.
- Rogers J.
- Rogers S.
- Rogers T.
- Rook C.
- Rooney L.
- Rosby E.
- Rose A.
- Rose Z.
- Ross I.
- Rothman A.
- Rothwell J.
- Roughley L.
- Rowan Kathryn
- Rowan N.
- Rowe A.
- Rowe N.
- Rowley M.
- Rudenko A.
- Rule R.
- Rushmer J.
- Ryan A.
- Ryan L.
- Ryan P.
- Rybka E.
- Ryder S.
- Salberg A.
- Saleh M.
- Salih H.
- Salman R.
- Salmon R.
- Sam M.
- Sam S.
- Saminathan S.
- Sammons E.
- Sammut D.
- Sampson J.
- Samuel M.
- Samuel Y.
- Sanchez Gonzalez A.
- Sanchez V.
- Sandercock Peter
- Sangombe M.
- Sanju M.
- Santosh R.
- Sarfatti A.
- Sarkar R.
- Sarwar Z.
- Sathyanarayanan L.
- Saunderson A.
- Scaletta D.
- Scanlon D.
- Scarratt L.
- Scattergood S.
- Schadenberg A.
- Schafers J.
- Schneblen W.
- Schofield E.
- Schumacher N.
- Schunke N.
- Scobie A.
- Scoones T.
- Scott A.
- Scott C.
- Scullion A.
- Seaton I.
- Sedano J.
- Segovia M.
- Selby F.
- Sellers K.
- Sen N.
- Sengupta A.
- Sewdin T.
- Seymour J.
- Shah H.
- Shah R.
- Shah S.
- Shaibu A.
- Shanahan T.
- Sharaf H.
- Sharma B.
- Sharma O.
- Sharma S.
- Sharp L.
- Sharratt P.
- Shaw D.
- Shaw J.
- Shawcross A.
- Shea D. O.
- Sheffield J.
- Shehata Z.
- Shenton J.
- Shepherd A.
- Shepherd K.
- Shepherd L.
- Sheppeard R.
- Sheridan H.
- Sheridan R.
- Sherwin S.
- Shibly S.
- Shiham F.
- Shilladay C.
- Shillitoe B.
- Shioi C.
- Shirley K.
- Shurlock J.
- Shurmer Jack
- Siamia L.
- Siddle E.
- Sime R.
- Simpson A.
- Simpson D.
- Simpson J.
- Simpson M.
- Simpson P.
- Sinclair S.
- Singh C.
- Singh S.
- Singhal P.
- Sithiravel S.
- Sivanadarajah S.
- Skaria A.
- Skehan N.
- Skinner T.
- Skinner V.
- Skorko A.
- Slack A.
- Slade H.
- Small E.
- Smallridge A.
- Smart B.
- Smith C.
- Smith E.
- Smith H.
- Smith J.
- Smith L.
- Smith M.
- Smith N.
- Smith P.
- Smith R.
- Smith S.
- Smith T.
- Smith V.
- Snell D.
- Sobande T.
- Sobrino Diaz A.
- Solly R.
- Soni G.
- Soor P.
- Soothill G.
- Soren J.
- Spiller W.
- Spring O.
- Squires G.
- Squires J.
- Squires R.
- Srinivasan R.
- Stagg W.
- Stanton A.
- Staplin Natalie
- Starnes D.
- Steer J.
- Stefania V.
- Stefanowska P.
- Stephens A.
- Stephensen D.
- Stephenson E.
- Sterrenburg M.
- Stevens W.
- Stevenson A.
- Stevenson S.
- Steward M.
- Stewart C.
- Stewart K.
- Stewart Richard
- Stickley J.
- Stirrup S.
- Stock S.
- Stockdale A.
- Stone B.
- Stone S.
- Storey I.
- Stratton E.
- Stratton J.
- Stubbs A.
- Stuttard M.
- Subudhi C.
- Sugden P.
- Sukumaran A.
- Sundar S.
- Surtees M.
- Sutherland R.
- Sutherland S.
- Sutu M.
- Swanson-Low C.
- Swart T.
- Swift E.
- Swist-Szulik K.
- Sykes D.
- Sykes E.
- Symon D.
- Syndercombe A.
- T-Michael H.
- Tadros M.
- Tague L.
- Tahir H.
- Tait J.
- Talbot P.
- Tallent R.
- Tallon B.
- Tanney C.
- Tanton E.
- Taribagil P.
- Tarr E.
- Tasiou A.
- Tate A.
- Taylor C.
- Taylor J.
- Taylor K.
- Taylor L.
- Taylor R.
- Taylor-Siddons M.
- Teasdale F.
- Teasdale J.
- Teasdale K.
- Tebbutt J.
- Telfer A.
- Tempany J.
- Tereszkowski-Kaminski R.
- Tewkesbury D.
- Thake M.
- Thakker M.
- Thamu B.
- Thet P.
- Thomas A.
- Thomas E.
- Thomas K.
- Thomas R.
- Thomas S.
- Thompson E.
- Thompson J.
- Thompson K.
- Thompson R.
- Thornton D.
- Thornton J.
- Thornton S.
- Thorpe S.
- Thrasyvoulou L.
- Thraves H.
- Thu-Ta P.
- Thwaites Guy
- Tilbey S.
- Timerick J.
- Timmins A.
- Tinkler H.
- Tipper J.
- Tivenan H.
- Todd S.
- Tohfa M.
- Toohey C.
- Topham K.
- Topping M.
- Tousis R.
- Trevelyan M.
- Trewick N.
- Truell R.
- Tsakiridou K.
- Tsang C.
- Tucker S.
- Tufail A.
- Tuff J.
- Tully R.
- Turbitt K.
- Turgut T.
- Turner G.
- Turner K.
- Turner S.
- Turner-Bone I.
- Turney S.
- Tyer A.
- UK National Institute for Health Research Clinical Research Network (for the RECOVERY Collaborative Group)
- Ul Haq M.
- Ul Hassan W.
- Underwood C.
- Unsworth A.
- Uriel Alison
- Usher R.
- Ustianowski A.
- Vankayalapati P.
- Van’t Hoff W.
- Varghese M.
- Varnier G.
- Vasu V.
- Vatish M.
- Veerasamy S.
- Velankar S.
- Vella N.
- Velugupati A.
- Venables I.
- Venditti M.
- Veres M.
- Vergnano S.
- Vernall R.
- Verula J.
- Vethanayagam N.
- Vettikumaran S.
- Victoria S.
- Vinay S.
- Vincent O.
- Vincent R.
- Vyras E.
- Wade P.
- Waite A.
- Walden A.
- Walker I.
- Walker K.
- Walker S.
- Wallace G.
- Wallendszus K.
- Wallis G.
- Walsh D.
- Walters J.
- Walton E.
- Walton O.
- Wang N.
- Wang R.
- Wang S.
- Warburton S.
- Ward J.
- Ward L.
- Ward R.
- Wardle S.
- Warmington J.
- Warner C.
- Warran S.
- Warren R.
- Warren Y.
- Warris Adilia
- Wasson E.
- Waterfall H.
- Waters D.
- Watson A.
- Watson E.
- Watson J. G. R.
- Watson L.
- Watson R.
- Watterson D.
- Watts M.
- Waugh V.
- Wayman E.
- Weatherhead M.
- Webb C.
- Webster I.
- Weerakoon R.
- Weetman M.
- Wei S.
- Welch J.
- Welch S.
- Wels R.
- Welters I.
- Welton R.
- Wentworth L.
- West R.
- West S.
- Western L.
- Westhead R.
- Weston H.
- Wetherill B.
- White A.
- Whitehead C.
- Whitehouse A.
- Whitehouse T.
- Whiteley J.
- Whiteley S.
- Whittaker E.
- Whittle H.
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- Wignall C.
- Wilcock D.
- Wilcock E.
- Wild S.
- Wilding L.
- Wilding P.
- Wildsmith T.
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- Xavier B.
- Yaqoob N.
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- Publication venue
- Nature Publishing Group
- Publication date
- Field of study
Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome
Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.
- Author
- Aaron Folsom
- Aaron Isaacs
- Abbas Dehghan
- Adebowale Adeyemo
- Adrienne Tin
- Afshin Parsa
- Aida Karina Dieffenbach
- Alan B. Weder
- Alan B. Zonderman
- Alan F. Wright
- Alan Go
- Alan R. Shuldiner
- Alanna C. Morrison
- Albert Hofman
- Albert V. Smith
- Albert W. Dreisbach
- Alena Stancakova
- Alex N. Parker
- Alexander Teumer
- Alexandre F. R. Stewart
- Alistair Hall
- Amy J. Swift
- Anders Hamsten
- Andre Franke
- Andre G. Uitterlinden
- Andreas Meinitzer
- Andreas Tomaschitz
- Andreas Ziegler
- Andres Metspalu
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- Andrew D. Johnson
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- Aroon D. Hingorani
- Asif Rasheed
- Atsushi Takahashi
- Aude Saint-Pierre
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- Augustine Kong
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- Bamidele Tayo
- Barbara Kollerits
- Barbara Ludwig
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- Ben A. Oostra
- Benedicte Stengel
- Benjamin F. Voight
- Benjamin J. Wright
- Bernhard K. Krämer
- Bernhard O. Böhm
- Bernhard Paulweber
- Bernhard R. Winkelmann
- Bo Hedblad
- Bok-Ghee Han
- Braxton D. Mitchell
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- D. G. Vinay
- Dabeeru C. Rao
- Daehee Kang
- Dag S. Thelle
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- Erwin P. Bottinger
- Eva Albrecht
- Eva Brand
- Ewa Zukowska-Szczechowska
- F. Gerald R. Fowkes
- Fadi J. Charchar
- Federico Murgia
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- Gunnar Jacobs
- Guo Li
- H-Erich Wichmann
- Haidong Zhu
- Hakon H. Hakonarson
- Halit Ongen
- Hans J. Rupprecht
- Hao Mei
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- Harold Snieder
- Harry Campbell
- Heather M. Stringham
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- Hilma Holm
- Hirotsugu Ueshima
- Holly Kramer
- Honghuang Lin
- Hua Tang
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- Hyung-Lae Kim
- I. Mateo Leach
- Ian Ford
- Ian H. de Boer
- Ian N. M. Day
- Ida Yii-Der Chen
- Idris Guessous
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- Jyotika K. Fernandes
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- Kari Stefansson
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- Louise V. Wain
- Lowell Satler
- Lude Franke
- Luigi Ferrucci
- Lyle J. Palmer
- Lynda M. Rose
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- Maciej Tomaszewski
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- null null
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- Petra Bruse
- Philip Howard
- Philipp S. Wild
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- Pim van der Harst
- Pio d’Adamo
- Qiong Yang
- Rainer Rettig
- Ramachandran S. Vasan
- Rebecca Hardy
- Reedik Mägi
- Reijo Laaksonen
- Reiner Biffar
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- Renate Schnabel
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- Tamara B. Harris
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- Tazeen H. Jafar
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- Terri L. Young
- Tetsuro Miki
- Themistocles L. Assimes
- Thomas F. Münzel
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- Thor Aspelund
- Thorsten Reffelmann
- Tien-Yin Wong
- Tiit Nikopensius
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- Timothy M. Frayling
- Tin Aung
- Toby Johnson
- Tom R. Gaunt
- Tomohiro Katsuya
- Tomonori Okamura
- Tonu Esko
- Toshihiro Tanaka
- Toshiko Tanaka
- Toshio Ogihara
- Tunde Salako
- Tune H. Pers
- Ulf Gyllensten
- Unnur Thorsteinsdottir
- Uwe Völker
- Valur Emilsson
- Vasyl Pihur
- Veikko Salomaa
- Veronique Vitart
- Vikal Tripathy
- Ville Aalto
- Vilmundur Gudnason
- Vincent Chouraki
- Vincent Mooser
- Viviane Nicaud
- Vladan Mijatovic
- W. H. Linda Kao
- Walter Palmas
- Wayne D. Rosamond
- Wei-Min Chen
- Weihua Zhang
- Wendy L. McArdle
- Wiek H. van Gilst
- Wilfried Renner
- Will T. Longstreth
- William Matthai
- Wilmar Igl
- Winfried März
- Wolfgang Koenig
- Wolfgang Lieb
- Wolfram Goessling
- Xiaofeng Zhu
- Xiaoling Wang
- Xiuqing Guo
- Xueling Sim
- Yali Li
- Yan V. Sun
- Yanbin Dong
- Yasuharu Tabara
- Yen-Pei C. Chang
- Yi-An Ko
- Yik-Ying Teo
- Ying A. Wang
- Ying Wu
- Yingchang Lu
- Yong Li
- Yongmei Liu
- Yoon Shin Cho
- Yoshikuni Kita
- Young Jin Kim
- Yuan-Tsong Chen
- Yukinori Okada
- Yuri Milaneschi
- Yurii Aulchenko
- Yusuke Nakamura
- Yvonne T. van der Schouw
- Zouhair Aherrahrou
- Åsa Johansson
- Publication venue
- Springer Nature America, Inc
- Publication date
- 27/10/2015
- Field of study
Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways