67 research outputs found
Diagnostic accuracy of the vegetative and minimally conscious state: Clinical consensus versus standardized neurobehavioral assessment
- Author
- A Shiel
- Audrey Vanhaudenhuyse
- B Jennett
- C Schnakers
- C Schnakers
- Caroline Schnakers
- EF Wijdicks
- G Teasdale
- Gustave Moonen
- H Gill-Thwaites
- J Giacino
- J Giacino
- Joseph Giacino
- JT Giacino
- K Andrews
- K Andrews
- M Boly
- Manfredi Ventura
- Melanie Boly
- NL Childs
- S Laureys
- S Majerus
- Steve Majerus
- Steven Laureys
- The Multi-Society Task Force on PVS
- Publication venue
- BioMed Central
- Publication date
- 01/01/2009
- Field of study
BACKGROUND: Previously published studies have reported that up to 43% of patients with disorders of consciousness are erroneously assigned a diagnosis of vegetative state (VS). However, no recent studies have investigated the accuracy of this grave clinical diagnosis. In this study, we compared consensus-based diagnoses of VS and MCS to those based on a well-established standardized neurobehavioral rating scale, the JFK Coma Recovery Scale-Revised (CRS-R). METHODS: We prospectively followed 103 patients (55 +/- 19 years) with mixed etiologies and compared the clinical consensus diagnosis provided by the physician on the basis of the medical staff's daily observations to diagnoses derived from CRS-R assessments performed by research staff. All patients were assigned a diagnosis of 'VS', 'MCS' or 'uncertain diagnosis.' RESULTS: Of the 44 patients diagnosed with VS based on the clinical consensus of the medical team, 18 (41%) were found to be in MCS following standardized assessment with the CRS-R. In the 41 patients with a consensus diagnosis of MCS, 4 (10%) had emerged from MCS, according to the CRS-R. We also found that the majority of patients assigned an uncertain diagnosis by clinical consensus (89%) were in MCS based on CRS-R findings. CONCLUSION: Despite the importance of diagnostic accuracy, the rate of misdiagnosis of VS has not substantially changed in the past 15 years. Standardized neurobehavioral assessment is a more sensitive means of establishing differential diagnosis in patients with disorders of consciousness when compared to diagnoses determined by clinical consensus
Cildb: a knowledgebase for centrosomes and cilia
- Author
- A Demertzi
- A Demertzi
- A Kubler
- A Shiel
- A Shiel
- A Vanhaudenhuyse
- A Vanhaudenhuyse
- A Vanhaudenhuyse
- A Vanhaudenhuyse
- A Vanhaudenhuyse
- A Zeman
- AM Owen
- American Congress of Rehabilitation Medicine
- AR Damasio
- B Baars
- B Jennett
- B Jennett
- B Wilhelm
- BJ Ansell
- BR Cant
- C Brefel-Courbon
- C Fischer
- C Schnakers
- C Schnakers
- C Schnakers
- C Schnakers
- C Schnakers
- C Schnakers
- C Schnakers
- D Nieuwenhuijs
- DE Levy
- DT Wade
- E Sellers
- E Wijdicks
- EA Fridman
- EF Wijdicks
- EF Wijdicks
- EG Zandbergen
- F Perrin
- F Plum
- G Deuschl
- G Teasdale
- GB Young
- H Gill-Thwaites
- H Oh
- HB Di
- HU Voss
- J Daltrozzo
- J Leon-Carrion
- J Whyte
- J Whyte
- J Whyte
- J-M Guérit
- JD Born
- JD Born
- JJ Fins
- JJ Fins
- JL Shames
- JS Lin
- JT Giacino
- JT Giacino
- K Andrews
- L Naccache
- M Boly
- M Boly
- M Boly
- M Boly
- M Bruno
- M Struys
- MA Passler
- MT Alkire
- ND Schiff
- ND Schiff
- ND Schiff
- NL Childs
- NM Kane
- O Gosseries
- O Stelt van der
- P Maquet
- P Qin
- P Tolle
- R Clauss
- R Clauss
- R Naatanen
- RD Zafonte
- RL Wood
- RP Clauss
- RP Clauss
- S Fang
- S Laureys
- S Laureys
- S Laureys
- S Laureys
- S Laureys
- S Laureys
- S Laureys
- S Laureys
- S Laureys
- S Laureys
- S Laureys
- S Laureys
- S Laureys
- S Laureys
- S Laureys
- S Laureys
- S Laureys
- S Majerus
- S Sutton
- SI Cohen
- SJ Dundon
- T Cochrane
- T Taira
- The Multi-Society Task Force on PVS
- The Quality Standards Subcommittee of the American Academy of Neurology
- Publication venue
- Oxford University Press
- Publication date
- 01/01/2011
- Field of study
Ciliopathies, pleiotropic diseases provoked by defects in the structure or function of cilia or flagella, reflect the multiple roles of cilia during development, in stem cells, in somatic organs and germ cells. High throughput studies have revealed several hundred proteins that are involved in the composition, function or biogenesis of cilia. The corresponding genes are potential candidates for orphan ciliopathies. To study ciliary genes, model organisms are used in which particular questions on motility, sensory or developmental functions can be approached by genetics. In the course of high throughput studies of cilia in Paramecium tetraurelia, we were confronted with the problem of comparing our results with those obtained in other model organisms. We therefore developed a novel knowledgebase, Cildb, that integrates ciliary data from heterogeneous sources. Cildb links orthology relationships among 18 species to high throughput ciliary studies, and to OMIM data on human hereditary diseases. The web interface of Cildb comprises three tools, BioMart for complex queries, BLAST for sequence homology searches and GBrowse for browsing the human genome in relation to OMIM information for human diseases. Cildb can be used for interspecies comparisons, building candidate ciliary proteomes in any species, or identifying candidate ciliopathy genes
Knowledge of Partial Awareness in Disorders of Consciousness: Implications for Ethical Evaluations?
- Author
- A Geremek
- A Owen
- A Owen
- B Gert
- B Williams
- D DeGrazia
- D Sturma
- D Sturma
- E Hildt
- E Racine
- F Jackson
- G Luf
- H Blumenfeld
- H Frankfurt
- H Gill-Thwaites
- H Noonan
- HB Di
- J Giacino
- J Levine
- J Locke
- JS Mill
- K Ameriks
- M Monti
- M Monti
- M Quante
- M Quante
- M Schroeder
- N Birbaumer
- N Block
- O Gosseries
- Orsolya Friedrich
- P Baumann
- P Carruthers
- P Singer
- P Thagard
- S Eickhoff
- S Laureys
- S Laureys
- S Shoemaker
- S Welie
- T Beauchamp
- T Mappes
- W Gehlen
- W Vossenkuhl
- Warren
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies
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- Abad R. D.
- Abe T.
- Abelha P.
- Abroug F.
- Adams J. C.
- Adamsson R. O.
- Adderly J.
- Adhikari A.
- Adolfsson A.
- Aguilar R. Z.
- Aguirre J. S.
- Aguirre S.
- Aguirre-Bermeo H.
- Ahsan A.
- Aisa T. M.
- Aisiku I.
- Ajetunmobi O. O.
- Akaraborworn O.
- Aker M.
- Akgun N.
- Akhtar A.
- Akyol O. O.
- Al Dorzi H. M.
- Al Jabbary A. S.
- Alam A. S.
- Albaiceta G. M.
- Albarrak M. M.
- Alberts E.
- Albiero D.
- Alda R. S.
- Alejandro R. V.
- Alexander P.
- Alfonso A. A. T.
- Algaba A.
- Algera A. G.
- Ali S. M.
- Aliaga F. A.
- Alisasis A. U.
- Allan R. M.
- Allue R. M.
- Almeida R. D. S.
- Almekhlafi G.
- Alonso J. G.
- Altaf W.
- Alvarez A. M.
- Alvarez J.
- Alves R. A.
- Alzugaray P.
- Amendola C. P.
- Amin P.
- Amir F.
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- Ampinelli A. M. R.
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- Andersen F. H.
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- Andruszkiewicz P.
- Aneman A.
- Anquez N.
- Antonelli M. M.
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- Aoki N.
- Appelberg H.
- Arabi Y.
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- Aragao D.
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- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2022
- Field of study
Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42\ub74% vs 44\ub72%; absolute difference \u20131\ub769 [\u20139\ub758 to 6\ub711] p=0\ub767; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5\u20138] vs 6 [5\u20138] cm H2O; p=0\ub70011). ICU mortality was higher in MICs than in HICs (30\ub75% vs 19\ub79%; p=0\ub70004; adjusted effect 16\ub741% [95% CI 9\ub752\u201323\ub752]; p<0\ub70001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0\ub780 [95% CI 0\ub775\u20130\ub786]; p<0\ub70001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status. Funding: No funding
Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls
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- Zhao B
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- Publication venue
- 'Elsevier BV'
- Publication date
- 27/03/2023
- Field of study
Background The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders
Cohort Profile: Post-Hospitalisation COVID-19 (PHOSP-COVID) study
- Author
- Abel K
- Adamali H
- Adeloye D
- Adeyemi O
- Adrego R
- Ahmad S
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- Publication venue
- Oxford University Press (OUP)
- Publication date
- 18/12/2023
- Field of study
Whole-genome sequencing reveals host factors underlying critical COVID-19
- Author
- Abd Elghafar M. S.
- Abdel-Aziz M.
- Abdelrazik M.
- Abdollahi H.
- Abdullah T.
- Abecasis G. R.
- Abedalthagafi M.
- Abel L.
- Abernathy C.
- Abraheem A.
- Abul-Husn N. S.
- Acquilini D.
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- Adanini O.
- Adeleye O.
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- Al-Afghani H.
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- Alaamery M.
- Alahmadey Z. Z.
- Alaverdian D.
- Alavere H.
- Albader A.
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- 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
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- 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
Germline variation at 8q24 and prostate cancer risk in men of European ancestry
- Author
- Adolfsson Jan
- Aguado Miguel
- Aitken Joanne
- Albanes Demetrius
- Alcaraz Antonio
- Aly Markus
- Andriole Gerald
- Aukim-Hastie Claire
- Auvinen Anssi
- Bangma Christopher
- Barnett Gill
- Batra Jyotsna
- Beane Freeman Laura E.
- Benlloch Sara
- Bensen Jeanette T.
- Bentzen Søren
- Berndt Sonja I.
- Berry Clare
- Bisbjerg Rasmus
- Bohnert Philipp
- Borre Michael
- Brenner Hermann
- Broms Michael
- Brook Mark N.
- Brown Paul
- Burnet Neil
- Bustamante Mariona
- Butler Lisa
- Calvo Patricia
- Cancel-Tassin Géraldine
- Cannon-Albright Lisa A.
- Canzian Federico
- Cao Guangwen
- Carballo Ana
- Cardoso Marta
- Carracedo Angel
- Carter Brian D.
- Castaño-Vinyals Gemma
- Castelao Jose Esteban
- Cavalli-Bjoerkman Carin
- Cecchini Lluís
- Cenee Sylvie
- Chambers Suzanne
- Chanock Stephen J.
- Christova Svetlana
- Claessens Frank
- Clements Judith
- Conti David V.
- Cook Margaret
- Cox Angela
- Cuk Katarina
- Cussenot Olivier
- Cybulski Cezary
- Dadaev Tokhir
- Davis Michael
- De Langhe Sofie
- De Meerleer Gert
- De Ruyck Kim
- Dearnaley David
- Dierssen-Sotos Trinidad
- Dikov Tihomir
- Ding Yuan Chun
- Donovan Jenny L.
- Drake Bettina F.
- Dunning Alison M.
- Easton Douglas F.
- Eckert Allison
- Eeles Rosalind A.
- Eklund Martin
- Elliott Rebecca
- Evans Andrew
- Fachal Laura
- Feng Ninghan
- Finelli Antonio
- Fisher Cyril
- Fitzgerald Liesel M.
- Fleshner Neil E.
- Freedman Matthew
- Gago-Dominguez Manuela
- Gamulin Marija
- Gapstur Susan M.
- Gardiner Robert
- George Anne
- Geybels Milan S.
- Giles Graham G.
- Giovannucci Edward
- Goodman Phyllis J.
- Govindasami Koveela
- Gracia-Lavedan Esther
- Grindedal Eli M.
- Grönberg Henrik
- Guo Jianming
- Guo Xin
- Guy Michelle
- Gómez Acebo Inés
- Gómez-Caamaño Antonio
- Haiman Christopher A.
- Hakansson Niclas
- Hamdy Freddie C.
- Hamilton Robert J.
- Hayes Vanessa
- Haynes Anne-Maree
- Hazel Steve
- He Weiyang
- Henderson Brian E.
- Herkommer Kathleen
- Hicks Belynda
- Holleczek Bernd
- Hoover Robert N.
- Hopper John L.
- Horvath Lisa
- Hunter David J.
- Hutchinson Amy
- Imai Takashi
- Ingles Sue A.
- Iversen Peter
- Jenster Guido
- Johansson Jan-Erik
- John Esther M.
- Joniau Steven
- Kachakova Darina
- Kaneva Radka
- Karlsson Ami
- Kastelan Zeljko
- Kedda Mary-Anne
- Kerns Sarah
- Key Tim J.
- Khaw Kay-Tee
- Kibel Adam S.
- Kierzek Andrzej
- Kim Jeri
- Klarskov Peter
- Klim Aleksandra
- Kluzniak Wojciech
- Kogevinas Manolis
- Kolb Suzanne
- Kolonel Laurence N.
- Kote-Jarai Zsofia
- Koudou Yves Akoli
- Koutros Stella
- Kraft Peter
- Kujala Paula
- Kulis Tomislav
- Kulkarni Girish S.
- Lane Athene
- Larkin Samantha
- Le Marchand Loic
- Lessel Davor
- Lewis Sarah J.
- Li Jie
- Li Meiling
- Lim Jasmine
- Lin Daniel W.
- Lin Hui-Yi
- Lin Ji
- Lindström Sara
- Ling Jin
- Livni Naomi
- Llorca Javier
- Lobato-Busto Ramón
- Logothetis Christopher J. J.
- Lophatananon Artitaya
- Lu Yong-Jie
- Lubinski Jan
- Luedeke Manuel
- Ma Jing
- Machiela Mitchell J.
- MacInnis Robert J.
- Maehle Lovise
- Maia Sofia
- Maier Christiane
- Mao Xueying
- Marsden Gemma
- Martin Richard M.
- Martinez Maria Elena
- Marzec Jacek
- Matejcic Marco
- McDonnell Shannon K.
- Menegaux Florence
- Mengual Lourdes
- Michael Agnieszka
- Milne Roger
- Mitev Vanio
- Mitkova Atanaska
- Morgan Angela
- Moya Leire
- Mucci Lorelei
- Muir Kenneth
- Mulot Claire
- Murtola Teemu
- Neal David E.
- Neuhausen Susan L.
- Newcomb Lisa F.
- Nielsen Sune F.
- Nordestgaard Børge G.
- Nordström Tobias
- Olama Ali Amin Al
- Ong Aik T.
- Orntoft Torben Falck
- Ost Piet
- Ostrander Elaine A.
- Ostrer Harry
- Pandha Hardev
- Papargiris Melissa
- Park Hyun
- Park Jong Y.
- Parliament Matthew
- Pashayan Nora
- Paulo Paula
- Pedersen John
- Peleteiro Paula
- Penney Kathryn L.
- Pharoah Paul
- Popov Elenko
- Pow-Sang Julio
- Ranu Hardeep
- Razack Azad
- Rebillard Xavier
- Ren Guoping
- Riboli Elio
- Risbridger Gail
- Riska Shaun
- Roobol Monique J.
- Rosenstein Barry
- Ruiz-Dominguez José Manuel
- Røder Martin Andreas
- Saito Shiro
- Sanchez Marie
- Saunders Edward J.
- Saunders Pamela
- Schaid Daniel J.
- Schleutker Johanna
- Schnoeller Thomas
- Schroder F. H.
- Schumacher Fredrick R.
- Sellers Thomas A.
- Sheng Xin
- Siddiq Afshan
- Silva Maria P.
- Sipeky Csilla
- Slavov Chavdar
- Sorensen Karina D.
- Southey Melissa C.
- Spurdle Amanda
- Srinivasan Srilakshmi
- Stampfer Meir
- Stanford Janet L.
- Stattin Par
- Steele Linda
- Stegmaier Christa
- Stern Mariana C.
- Stevens Victoria L.
- Strom Sara S.
- Sun Zan
- Szulkin Robert
- Taari Kimmo
- Talala Kirsi
- Tammela Teuvo L. J.
- Tan Meng H.
- Tangen Catherine M.
- Taylor Renea
- Teixeira Manuel R.
- Teo Soo-Hwang
- Thibodeau Stephen N.
- Thierens Hubert
- Thompson Ian M.
- Thwaites Alison
- Tilley Wayne
- Tillmans Lori
- Toi Ants
- Townsend Paul A.
- Travis Ruth C.
- Tretarre Brigitte
- Truong Thérèse
- Turman Constance
- Usmani Nawaid
- Van den Broeck Thomas
- van der Kwast Theodorus H.
- van Schaik Ron H. N.
- Vega Ana
- Vlahova Aleksandrina
- Vogel Walther
- Vogt Aurelie
- Wang Guomin
- Wang Kan
- Weinstein Stephanie
- Weisher Maren
- West Catharine
- Whitmore Ian
- Wiklund Fredrik
- Wokolorczyk Dominika
- Wolk Alicja
- Wu Huihai
- Wu Ji
- Wu Yudong
- Xu Jianfeng
- Yeadon Trina
- Yu Yongwei
- Zachariah Babu
- Zhang Hong-Wei
- Zhang Yangling
- Zhao Shan-Chao
- Zhou Bo
- Zlotta Alexandre R.
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2018
- Field of study
Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification
Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity
- Author
- 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. 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. Easthorpe
- 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. Noakes
- A. Patel
- A. Pickard
- 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 Brown
- Adam Krętowski
- Adriana Roży
- Agnese Verzuri
- Agnieszka Adamek
- Agnieszka Bielska
- Agostino Ognibene
- Agostino Riva
- Ailsa Golightly
- Alan Maclean
- Albert Tenesa
- Aleksandra Berkan-Kawinska
- Aleksandra Jezela-Stanek
- Aleksandra Starosz
- Alessandra Guarnaccia
- Alessandra Renieri &
- Alessandra Stella
- Alessandra Vergori
- Alessandro Pancrazzi
- Alessia Giorli
- Alice Donati
- Alison Meynert
- Alistair Nichol
- Anders Larsson
- Andrea Antinori
- Andrea Cossarizza
- Andrea Gabbuti
- Andrea Tommasi
- Andrew D. Bretherick
- Andrew Law
- Andrew Stenhouse
- Andrzej Eljaszewicz
- Andrzej Horban
- Andy Law
- Angelica Pagliazzi
- Angie Fawkes
- Anke Hinney
- Anna Canaccini
- Anna Kruk
- Anna Maria Pinto
- Anna Moniuszko-Malinowska
- Anna Parfieniuk-Kowerda
- Anna Piekarska
- Anna Szałkowska
- Annarita Giliberti
- Anne Richmond
- Antonella D. ’Arminio Monforte
- Antonella Vincenti
- Antonia Ho
- Antonio Di Biagio
- Antonio Perrella
- Arianna Emiliozzi
- Arianna Gabrieli
- Arsalin Azzadin
- Asma Al Thani &
- Athanasios Kousathanas
- Audrey Coutts
- Axel Schmidt
- Axel Schmidt
- 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. Johnson
- 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
- Barbara Rossetti
- Barbara Shih
- Barbara Sobala-Szczygiel
- Beata Puzanowska
- Benedetta Romanin
- Björn Jensen
- Bo Wang
- Brent Richards
- 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. Eastgate
- C. Finch
- C. Gibson
- C. Gorman
- C. Hays
- C. Hewitt
- C. Holl
- C. Howcroft
- C. Humphrey
- C. Jackson
- C. Jardine
- C. Jennings
- C. Jones
- C. Kaye
- C. Lynch
- C. Lyons
- C. McCulloch
- C. McParland
- C. McParland
- C. Murphy
- C. Parmar
- C. Pawley
- C. Phillips
- C. Phillips
- C. Pothecary
- C. Pothecary
- C. Prendergast
- C. Price
- C. Rishton
- C. Shovelton
- C. Sicat
- C. Stuart
- C. Summers
- C. Swan
- C. Thompson
- C. Thorpe
- C. Tibke
- C. Tierney
- C. Vigurs
- C. Wells
- C. Whitton
- C. Whyte
- C. Wrey Brown
- Carlo Maj
- Carmelo Piscopo
- Caroline Abernathy
- Caterina Lo Rizzo
- Ce Dunmore
- Cecilia Costa
- Ceilia Boz
- Cesira Nencioni
- Chadi Saad
- Charles Hinds
- Charlotte Summers
- Chenqing Zheng
- Chiara Barbieri
- Chiara Fallerini
- Chiara Gabbi
- Chiara Spertilli Raffaelli
- Chris P. Ponting
- Chris Ponting
- Christian Herr
- Christof Winter
- Christoph D. Spinner
- Clark D. Russell
- Claudia Suardi
- Claudio Ferri
- Clemens M. Wendtner
- 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. Golden
- D. Griffin
- 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
- Danilo Tacconi
- Danny McAuley
- David Bennett
- David Harrison
- David Maslove
- Davide Grassi
- Davide Romani
- Dawn Law
- Diana Alaverdian
- Diana Martonik
- Diego Ripamonti
- Domenico A. Coviello
- Dorota Pasko
- Dorota Zarębska-Michaluk
- E. Abaleke
- E. Allan
- E. Anastasescu
- E. Andrews
- E. Apetri
- 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. Jude
- 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. Salciute L. Grauslyte
- E. Smith
- E. Smithson
- E. Stoddard
- E. Stones
- E. Thomas
- E. Tilney
- E. Timlick
- E. Treus Gude
- E. Virgilio
- E. Watson
- E. Wilby
- E. Wraith
- Edoardo Conticini
- Elena Andreucci
- Elena Bargagli
- Elena Desanctis
- Elisa Benetti
- Elisa Frullanti
- Elisabetta Menatti
- Elisabetta Schiaroli
- Ellie Mcmaster
- Elvina Gountouna
- Emanuele Catena
- Enrico Cabri
- Enrico Martinelli
- Erika Fiorentini
- Erola Pairo-Castineira
- Erola Pairo-Castineira
- Esther Duncan
- Eugenia Quiros-Roldan
- Eva C. Schulte
- Eva C. Schulte
- 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
- Fabian Brand
- Fabio Lena
- Faisal Almalki
- Federica Gaia Miraglia
- Federico Anedda
- Federico Franchi
- Ferdinando Giannattasio
- Filip Taneski
- Filippo Aucella
- Filippo Biscarini
- Fiona Griffiths
- Floriana Valentino
- Francesca Andretta
- Francesca Ariani
- Francesca Colombo
- Francesca Fava
- Francesca Gatti
- Francesca Mari
- Francesca Minnai
- Francesca Montagnani
- Francesca Vichi
- Francesco Bianchi
- Francesco Brancati
- Francesco Castelli
- Francesco Menichetti
- Francesco Paciosi
- Francesco Raimondi
- Francesco Vladimiro Segala
- Francis P. Crawley
- Franco Maggiolo
- Franco Marinangeli
- 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. Randell
- G. Sadera
- G. Seddon
- G. Sera Howe
- G. Sloane
- G. Subramanian
- G. Tsinaslanidis
- G. Turner
- G. Watson
- G. Wray
- Gabriela Sokołowska
- Gabriella Coiro
- Gabriella Doddato
- Gabriella Maria Squeo
- GEN-COVID Multicenter Study
- Genni Spargi
- GenOMICC Consortium
- Giada Beligni
- Gian Piero Caldarelli
- Gianfranco Parati
- Giovanna Morelli
- Giulia Gori
- Giuseppe Fiorentino
- Giuseppe Merla
- Giusy Tiseo
- Graeme Grimes
- Guillaume Butler-Laporte
- Guillaume Butler-Laporte
- H. Bancroft
- H. Bates
- H. Belfield
- H. Blackman
- H. Blakemore
- H. Brooke
- H. Button
- H. Coles
- H. Curgenven
- H. Filipe
- H. Fox
- H. Golding
- H. Hill
- H. Holcombe
- H. Houlden
- H. Jeffrey
- H. Kent
- H. Langton
- H. McGuinness
- H. Meghari
- H. Millward
- H. Moore
- H. Parker
- H. Prady
- H. Quinn
- H. Rangarajan
- H. Rehman
- H. Reschreiter
- H. Riley
- H. Sainsbury
- H. Savill
- H. Sturgeon
- H. T-Michael
- H. Tench
- H. Tiveran
- H. Turner
- H. Whittle
- H. Willis
- H. Wood
- Hadeel AlBardis
- Hamdi Mbarek
- Hanning Mal
- Helen Szoor-McElhinney
- Hugh Montgomery
- Hugo Zeberg
- Hugo Zeberg
- 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. Otaha
- I. Otahal
- I. Turner-Bone
- I. Welters
- I. White
- I. Wynter
- Ilaria Meloni
- Ilaria Rancan
- Immacolata Andolfo
- Isabella Zanella
- Iwona Mozer-Lisewska
- J. Allan
- J. Barker
- J. Bewley
- J. Biddle
- J. Birch
- J. Birch
- J. Bradley-Potts
- J. Brent Richards
- J. brown
- J. Bryant
- J. Butler
- J. Camsooksai
- J. Camsooksai
- J. Carter
- J. Caterson
- J. Cebrian Suarez
- J. Cockerill-Taylor
- J. Cole
- J. Colley
- J. Cooper
- J. Cupitt
- J. Cuttler
- J. Daglish
- J. Dawson
- J. Dearden
- J. Deery
- J. Donnachie
- J. Dykes
- J. Easton
- J. Fernandez Roman
- J. Finn
- J. Fletcher
- J. Frankham
- J. Gaylard
- J. Gill
- J. Godden
- J. Goodsell
- J. Gregory
- J. Greig
- J. Gurasashvili
- J. Hardy
- J. Harris
- J. Hatton
- J. Hawes
- J. Highgate
- J. Hornsby
- J. Hulme
- J. Hunt
- J. Hutter
- J. Ingham
- J. Jones
- J. Jones
- J. K. Baillie
- J. Kassam
- J. Kenneth Baillie
- J. Kenneth Baillie
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- T. Williams
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- Tammy Gilchrist
- Thorsten Brenner
- Tim Walsh
- Tiziana Bachetti
- Tomas Luther
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- Tony Wackett
- Torsten Feldt
- Trevor Paterson
- Tullio Trotta
- U. Poultney
- Ulrike Protzer
- Umberto Zuccon
- Urszula Korotko
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- Urszula Polowianiuk
- V. Amin
- V. Anumakonda
- V. Bastion
- V. Cannons
- V. Crickmore
- V. Gopal
- V. Irvine
- V. Kasipandian
- V. Krishnamurthy
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- V. Sarathy
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- Valentina Anemoli
- Valentina Borgo
- Valentina Perticaroli
- Verena Keitel
- Veronique Vitart
- W. Harrison
- W. Khaliq
- W. Khaliq
- W. McCormick
- W. Woodyatt
- Wadha Al-Muftah
- WES/WGS Working Group Within the HGI
- Wiktoria Izdebska
- Wilna Oosthuyzen
- X. Qiu
- Xia Shen
- Y. Baird
- Y. Choudhury
- Y. Hussain
- Y. Jackson
- Y. Thirlwall
- Yanara Marincevic-Zuniga
- Yang Wu
- Yaser Al-Sarraj
- Z. Alldis
- Z. Belagodu
- Z. Bradshaw
- Z. Coton
- Z. Daly
- Z. Farzad
- Z. Fernandez
- Z. Garland
- Z. Maqsood
- Z. Omar
- Z. Prime
- Z. Scott
- Zhijian Yang
- Publication venue
- Publication date
- 01/01/2022
- Field of study
The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)
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