5 research outputs found
Valor predictivo de la puntuación SYNTAX en la lesión vascular culpable y no culpable. Respuesta
- Publication venue
- 'Elsevier BV'
- Publication date
- 23/03/2017
- Field of study
info:eu-repo/semantics/publishedVersio
Stroke genetics informs drug discovery and risk prediction across ancestries
- Author
- Aamodt AH
- Abedi V
- Adams H
- Adebajo OJ
- Adeoye AM
- Afzal S
- Ago T
- Agunloye A
- Akinyemi J
- Akinyemi R
- Akpa O
- Akpalu A
- Almgren P
- Amin N
- Amouyel P
- Anderson CD
- Anderson CD
- Aparicio HJ
- Arenillas JF
- Armasu SM
- Armstrong ND
- Arnett DK
- Arulogun O
- Attia J
- Ay H
- Bae H-J
- Bakker MK
- Bammler TK
- Bartz TM
- Bastarache L
- Beiser AS
- Beiser AS
- Bell S
- Benavente OR
- Benn M
- Bennett DA
- Berr C
- Bevan S
- Bis JC
- Bis JC
- Blay N
- Boerwinkle E
- Boncoraglio GB
- Bordes C
- Braekkan SK
- Brody JA
- Brouwers PJAM
- Brown RD
- Brumpton BM
- Brumpton BM
- Buring JE
- Bustamante M
- Butterworth AS
- Børte S
- Cain A
- Campos F
- Camps-Renom P
- Caro I
- Carrera C
- Carty CL
- Caso V
- Castillo J
- Chasman DI
- Chauhan G
- Chen J
- Chen M-H
- Chen P-H
- Chen W-M
- Chen WM
- Chen Y
- Chen Z
- Cheng Y-C
- Cho K
- Choi SH
- Chong MR
- Chowhan A
- Christensen K
- Clarke R
- Cole JW
- Collins R
- Correa A
- Cotlarciuc I
- Cruchaga C
- Cullell N
- Curtze S
- Cushman M
- Cárcel-Márquez J
- Damrauer SM
- Danesh J
- Dartigues J-F
- De Andrade M
- De Bakker PIW
- De Cid R
- De Cid R
- De Jager PL
- De Jager PL
- De Kort PL
- De Laat KF
- De Leeuw F-E
- De Leeuw F-E
- Debette S
- Delavaran H
- Deleuze J-F
- Delgado P
- Delgado P
- Delgado-Mederos R
- Den Heijer T
- Den Hoed M
- DeStefano AL
- Dhar R
- Diaz-Navarro R
- Dichgans M
- Duan Q
- Dörr M
- Ellekjær H
- Endres M
- Engelter ST
- Engström G
- Esko T
- Evans MK
- Fairhurst-Hunter Z
- Fakunle AG
- Falcone GJ
- Fernández-Cadenas I
- Ferreira LE
- Ferreira LE
- Fongang B
- Ford I
- Fornage M
- Frantz S
- França PHC
- Frazer KA
- Freijó M
- Frikke-Schmidt R
- Fritsche LG
- Furie KL
- Gabrielsen ME
- Gabrielsen ME
- Gallego-Fabrega C
- Gasca NC
- Gasca NC
- Geerlings MI
- Geerlings MI
- Georgakis MK
- Germain M
- Ghanbari M
- Gieger C
- Giese A-K
- Giese A-K
- Giulianini F
- Gons RAR
- Gordon W
- Gottesman RF
- Gottesman RF
- Gottesman RF
- Grabe HJ
- Gravel S
- Gretarsdottir S
- Grewal RP
- Gudnason V
- Gudnason V
- Guo Y
- Gurpreet WS
- Gustafsson S
- Habib N
- Hachiya T
- Haessler J
- Haessler J
- Haeusler KG
- Hagen K
- Hamsten A
- Hansen J-B
- Harris TB
- Hassan A
- Hata J
- Havulinna AS
- He J
- He Y
- Heath AK
- Heath AK
- Heckbert SR
- Heit JA
- Heitsch L
- Heuch I
- Heuschmann PU
- Hill M
- Ho Y-L
- Holliday EG
- Hopewell JC
- Howard G
- Howson JMM
- Hozawa A
- Hsu F-C
- Huffman JE
- Hveem K
- Hveem K
- Hyacinth HI
- Ibañez L
- Ibrahim M
- Ikram MA
- Ikram MK
- Ilinca A
- Ingelsson E
- Ingelsson M
- Inouye M
- Irvin MR
- Irvin MR
- Iwasaki M
- Jackson RD
- Jackson RD
- Jacob MA
- Jee YH
- Jenkins C
- Jensen GB
- Jeon CE
- Jern C
- Jian X
- Jiménez-Conde J
- Johnson AD
- Johnson JA
- Jood K
- Jousilahti P
- Judy RL
- Jukema JW
- Jung KJ
- Jürgenson T
- Kabrhel C
- Kaffashian S
- Kalra L
- Kamanu FK
- Kamatani Y
- Kamouchi M
- Kamstrup PR
- Kanai M
- Kappelle LJ
- Keene KL
- Kim B-J
- Kim J
- Kim YJ
- Kinnunen J
- Kissela BM
- Kitazono T
- Kittner SJ
- Kjartansson O
- Kleindorfer DO
- Kleinschnitz C
- Kloss M
- Knol MJ
- Koido M
- Komolafe M
- Konuma T
- Kooperberg C
- Kooperberg C
- Koudstaal PJ
- Kraft P
- Krebs K
- Kristoffersen ES
- Krupinski J
- Kubo M
- Kumar A
- Kõrv J
- Labovitz DL
- Lacaze P
- Lange LA
- Langefeld CD
- Langenberg C
- Lathrop GM
- Launer LJ
- Laurie CC
- Le Grand Q
- Le Grand Q
- Lee J-M
- Lee K-J
- Lee T-H
- Lemmens R
- Lemmons R
- Leonard HL
- Lepik K
- Levi CR
- Lewis AJ
- Lewis CM
- Leys D
- Li J
- Li L
- Li L
- Liaw Y-C
- Liaw Y-P
- Liman T
- Lin K
- Lin W-Y
- Lind L
- Lindgren AG
- Lindgren CM
- Lindstrom S
- Linkohr B
- Lioutas V
- Liu YM
- Lledós M
- Llucià-Carol L
- Longstreth WT
- Lopez OL
- Lopez-Cancio E
- Lorentzen E
- Luijckx G-J
- Lv J
- MacDonald J
- Magnusson PK
- Maguire J
- Makoto H
- Malik R
- Manichaikul A
- Markus HS
- Marston NA
- Martinez-Majander N
- Martinsen AE
- Martí-Fàbregas J
- Matsuda K
- Mayerhofer E
- McArdle PF
- McCauley BM
- McDonough CW
- McKnight B
- Meitinger T
- Melander O
- Menon V
- Meschia JF
- Metspalu A
- Milani L
- Millwood IY
- Millán M
- Minegishi N
- Mishra A
- Mitchell BD
- Molina CA
- Montaner J
- Montellano FA
- Morange P-E
- Morisaki T
- Morris AP
- Mosley TH
- Muiño E
- Murakami Y
- Muñoz-Narbona L
- Mägi R
- Müller-Nurasyid M
- Nagai A
- Nalls MA
- Namba S
- Nederkoorn PJ
- Nederkoorn PJ
- Nelis M
- Nielsen JB
- Nielsen JB
- Niiranen TJ
- Ninomiya T
- Nordestgaard BG
- Nordestgaard BG
- Norrving B
- Nygaard M
- Obach V
- Obiako R
- Ogbole G
- Ogishima S
- Okada Y
- Olalere A
- Onland-Moret NC
- Onland-Moret NC
- Osaigbovo G
- Ovbiagele B
- Owolabi L
- Owolabi MO
- O’Donnell CJ
- O’Donnell MJ
- Pankow JS
- Pankratz N
- Parati EA
- Parodi L
- Paré G
- Pattee JW
- Peddareddygari LR
- Pedersen LM
- Pedersen NL
- Pera J
- Perola M
- Peters A
- Peto R
- Pezzini A
- Pileggi S
- Posner DC
- Pozarickij A
- Prasad K
- Prats-Sánchez L
- Psaty BM
- Pulit SL
- Putaala J
- Puurunen MK
- Rabionet R
- Rannikmäe K
- Reiner A
- Reiner AP
- Rexrode KM
- Riaz M
- Riba-Llena I
- Ribasés M
- Ribó M
- Rice K
- Rich SS
- Ridker PM
- Rissanen IL
- Rolfs A
- Romero JR
- Roquer J
- Rosand J
- Rosendaal FR
- Roshchupkin GV
- Ross OA
- Rost NS
- Rothwell PM
- Rotter JI
- Rudd AG
- Ruff CT
- Ruigrok YM
- Rundek T
- Rutten-Jacobs L
- Sabatine MS
- Sacco RL
- Saillour-Glenisson F
- Sakaue S
- Sale MM
- Saleheen D
- Salomaa V
- Sandset EC
- Sanghera DK
- Sapkota BR
- Sarfo FS
- Sargurupremraj M
- Sargurupremraj M
- Sarin A-P
- Sarju R
- Sarnowski C
- Sasaki M
- Satizabal CL
- Satoh M
- Sattar N
- Sawada N
- Schmidt CO
- Schmidt D
- Schmidt R
- Schminke U
- Schnohr P
- Segura T
- Serrano-Heras G
- Seshadri S
- Sharma P
- Shi M
- Shimizu A
- Shiroma EJ
- Sibolt G
- Sigurdsson S
- Sigurdsson Á
- Simonsick EM
- Skogholt AH
- Sloane KL
- Slowik A
- Smith A
- Smith EN
- Smith NL
- Sobrino T
- Sobue K
- Soderholm M
- Soriano-Tárraga C
- Srinivasasainagendra V
- Stanne TM
- Stefansson K
- Stevens B
- Stine OC
- Stott DJ
- Strauch K
- Strbian D
- Suchon P
- Sudlow CLM
- Sumoy L
- Sun YV
- Sung YJ
- Sutoh Y
- Takai T
- Tanaka H
- Tang W
- Tanislav C
- Tanno K
- Tatlisumak T
- Taylor KD
- Taylor KD
- Teumer A
- Thijs VNS
- Thomas LF
- Thomassen JQ
- Thorleifsson G
- Thorsteinsdottir U
- Tiainen M
- Tiedt S
- Tiwari HK
- Tomppo L
- Torres-Aguila NP
- Touze E
- Traylor M
- Trompet S
- Trégouët D-A
- Tsugane S
- Tuladhar AM
- Turman C
- Turnbull I
- Tybjærg-Hansen A
- Tzourio C
- Uitterlinden AG
- Ungethüm K
- Uvere E
- Valdimarsson EM
- Van der Laan SW
- Van der Lee SJ
- Van Dijk EJ
- Van Dijk GW
- Van Duijn CM
- Van Hylckama Vlieg A
- Van Norden AGW
- Van Oostenbrugge RJ
- Van Rooij FGW
- Van Setten J
- Van Vugt M
- Van Vugt M
- Vaura FC
- Verma SS
- Verma SS
- Vermeer SE
- Vibo R
- Visser MC
- Vives-Bauza C
- Vonk JMJ
- Völker U
- Völzke H
- Wahab K
- Wakai K
- Walters M
- Walters RG
- Wang C
- Wang L
- Wang R
- Wareham NJ
- Wassertheil-Smoller S
- Weir D
- Wennberg P
- Wermer MJH
- Wiggins KL
- Willer CJ
- Williams SR
- Wilson JG
- Wilson PWF
- Winsvold BS
- Wolfe CDA
- Wong Q
- Woo D
- Worrall BB
- Xu H
- Yaffe K
- Yamaji T
- Yang C
- Yang C
- Yang Q
- Yonova-Doing E
- Yoon K
- Yu C
- Yusuf S
- Zand R
- Zhou W
- Zonderman AB
- Zwart J-A
- Álvarez-Sabín J
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 29/07/2022
- Field of study
Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries
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Demonstration of event position reconstruction based on diffusion in the NEXT-white detector
- Author
- Adams C
- Almazán H
- Aparicio B
- Aranburu AI
- Arazi L
- Arnquist IJ
- Auria-Luna F
- Ayet S
- Azevedo CDR
- Bailey K
- Ballester F
- Barrio-Torregrosa M del
- Bayo A
- Benlloch-Rodríguez JM
- Borges FIGM
- Brodolin A
- Byrnes N
- Carrión JV
- Cebrián S
- Church E
- Cid L
- Conde CAN
- Contreras T
- Cossío FP
- Cárcel S
- Dey E
- Dickel T
- dos Santos JMF
- Díaz G
- Elorza M
- Escada J
- Esteve R
- Felkai R
- Fernandes LMP
- Ferrario P
- Ferreira AL
- Foss FW
- Freitas EDC
- Freixa Z
- Generowicz J
- Goldschmidt A
- González R
- Grocott J
- Guenette R
- Gómez-Cadenas JJ
- Haefner J
- Hafidi K
- Hauptman J
- Henriques CAO
- Herrero V
- Herrero-Gómez P
- Hervés Carrete C
- Ifergan Y
- Jones BJP
- Labarga L
- Larizgoitia L
- Larumbe A
- Lebrun P
- Lopez F
- López-March N
- Madigan R
- Mano RDP
- Marques AP
- Martín-Albo J
- Martínez-Lema G
- Martínez-Vara M
- Meziani ZE
- Miller RL
- Mistry K
- Molina-Canteras J
- Monrabal F
- Monteiro CMB
- Mora FJ
- Morata JA Hernando
- Muñoz Vidal J
- Navarro KE
- Novella P
- Nuñez A
- Nygren DR
- Oblak E
- Palacio J
- Palmeiro B
- Para A
- Parmaksiz I
- Pelegrin J
- Pérez Maneiro M
- Querol M
- Redwine AB
- Renner J
- Rivilla I
- Rodríguez J
- Rogero C
- Rogers L
- Romeo B
- Romo-Luque C
- Santos FP
- Shomroni I
- Simón A
- Tripathi A
- Álvarez V
- Publication venue
- eScholarship, University of California
- Publication date
- 01/01/2024
- Field of study
Noble element time projection chambers are a leading technology for rare event detection in physics, such as for dark matter and neutrinoless double beta decay searches. Time projection chambers typically assign event position in the drift direction using the relative timing of prompt scintillation and delayed charge collection signals, allowing for reconstruction of an absolute position in the drift direction. In this paper, alternate methods for assigning event drift distance via quantification of electron diffusion in a pure high pressure xenon gas time projection chamber are explored. Data from the NEXT-White detector demonstrate the ability to achieve good position assignment accuracy for both high- and low-energy events. Using point-like energy deposits from 83mKr calibration electron captures (E∼45 keV), the position of origin of low-energy events is determined to 2 cm precision with bias <1mm. A convolutional neural network approach is then used to quantify diffusion for longer tracks (E≥1.5 MeV), from radiogenic electrons, yielding a precision of 3 cm on the event barycenter. The precision achieved with these methods indicates the feasibility energy calibrations of better than 1% FWHM at Qββ in pure xenon, as well as the potential for event fiducialization in large future detectors using an alternate method that does not rely on primary scintillation
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GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19
- Author
- Abdelrazik M
- Abedalthagafi M
- Abel L
- Abel L
- Abellan J
- Abernathy C
- Abraheem A
- Acklery A
- Acosta-Isaac R
- Adam R
- Adams C
- Adams K
- Adams N
- Adanini O
- Afolabi D
- Agasou A
- Agravante K
- Agravante K
- Agrawal S
- Aguado JM
- Aguilar C
- Aguilar PM
- Aguilera-Albesa S
- Ahmad N
- Ahmadhaider N
- Ahmed A
- Ahmed C
- Aitkin E
- Akeroyd L
- Akhtar MN
- Akinkugbe O
- Al-Moasseb H
- Alasdair F
- Alba J
- Albu S
- Alcalá-Gallardo KAM
- Alcoba-Florez J
- Aldridge J
- Alex B
- Alexander P
- Alfonso J
- Algarin-Lara HR
- Ali A
- Ali HH
- Ali IAM
- Ali S
- Allan A
- Allan E
- Allan J
- Alldis Z
- Allen L
- Allen M
- Allen S
- Allibone S
- Allison KS
- Ally SM
- Almadana V
- Almaden-Boyle C
- Almeida J
- Almoguera B
- Alonso MR
- Altabaibeh A
- Alvarez N
- Alvaro A
- Alves MDM
- Amamio M
- Amamio M
- Amin V
- Anastasescu E
- Anderson J
- Anderson M
- Anderson P
- Anderson S
- Anderson S
- Anderson T
- Andreou P
- Andreu-Bernabeu Á
- Andrew A
- Andrew B
- Andrew G
- Andrews J
- Andrikopoulos P
- Antcliffe D
- Antoine P
- Antonijoan MR
- Antony S
- Anumakonda V
- Anwer M
- Apetri E
- Aquino M
- Arana-Arri E
- Aranda C
- Arango C
- Araque C
- Araujo IMT
- Araujo NK
- Aravindan L
- Arbane G
- Arcanjo AC
- Archer K
- Arden T
- Arias SS
- Arif S
- Armistead J
- Armstrong D
- Armstrong L
- Armstrong R
- Arnaiz A
- Arnott A
- Arora M
- Arranz MJ
- Artiga M-J
- Ashby K
- Ashok SR
- Ashraf S
- Ashton L
- Aslibekyan S
- Astin-Chamberlain R
- Atayeva N
- Attwood B
- Atwal I
- Auld F
- Austin K
- Austin P
- Auton A
- Avello-Malaver Y
- Ayers A
- Ayuso C
- Bach B
- Badal B
- Baddeley A
- Bafitis V
- Baikady RR
- Bailey L
- Baillie JK
- Baillie JK
- Baillie K
- Baines D
- Baines K
- Baird T
- Baird Y
- Baker M
- Bakthavatsalam D
- Baldión-Elorza AM
- Bamford A
- Bamford A
- Bamford P
- Banach D
- Bancroft H
- Bandla N
- Bano S
- Baptista D
- Baptista-Rosas RC
- Barber R
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- Barberis L
- Barclay C
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- Barclay WS
- Barker J
- Barker M
- Barnes N
- Barr J
- Barranco-Díaz A
- Barreda-Sánchez M
- Barrera-Penagos V
- Barrett F
- Barron A
- Barrow E
- Barry P
- Bartley S
- Barton J
- Baruah R
- Bashyal A
- Basikolo C
- Bastion V
- Bates H
- Bates M
- Batres SA
- Battle C
- Bauchmuller K
- Baxter N
- Baxter-Dore S
- Bayo L-A
- Beadle J
- Bean S
- Beasley A
- Beaumont K
- Beavis S
- Beech E
- Beech V
- Beekes M
- Beer S
- Beesley K
- Begg C
- Behan T
- Beith C
- Beith C
- Belagodu Z
- Belfield H
- Belhassen-Garcia M
- Bell D
- Bell G
- Bell J
- Bell M
- Bell S
- Bellamy M
- Bellini A
- Bellwood R
- Bemand T
- Benham L
- Benito HG
- Benkenstein S
- Bennett S
- Bentley M
- Benyon S
- Beranova E
- Bercades G
- Bernal E
- Bernal-Bello D
- Bevan E
- Bewley J
- Bezerra JF
- Bezerra MAC
- Bhatia N
- Bhatterjee R
- Bhuie P
- Bi R
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- Biddle J
- Biggs H
- Birch J
- Birch J
- Birch S
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- Birchall K
- Birchall K
- Bircham S
- Bird S
- Birkinshaw I
- Birt M
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- Bishop L
- Biss J
- Black C
- Black E
- Black K
- Blackledge B
- Blackledge B
- Blackman H
- Blakemore H
- Blanca-López N
- Blancas R
- Bland Y
- Blow S
- Blowing H
- Blunt M
- Board S
- Bociek A
- Bogaert D
- Boix-Palop L
- Bokhari M
- Bolger A
- Bolger C
- Bolton M
- Bolton R
- Boltwood K
- Bonner S
- Bonnici J
- Booker L
- Borislavova B
- Borja AL
- Borobia A
- Borra C
- Botello A
- Botfield D
- Botfield L
- Bough L
- Bowes A
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- Bowles R
- Bowman F
- Boxall H
- Boyd E
- Boyer N
- Boyle P
- Boyle R
- Boz C
- Bradley C
- Bradley P
- Bradley-Potts J
- Bradley-Potts J
- Bradshaw Z
- Brady A
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- Brady M
- Brady R
- Brandwood C
- Brandwood C
- Branney D
- Bravo E
- Brayne A
- Brealey D
- Brealey D
- Brearey S
- Bremmer P
- Bretherick AD
- Brett M
- Brett S
- Brickell K
- Bridgett V
- Brimfield L
- Brinkworth E
- Brion M
- Briton K
- Briton K
- Brochado-Kith Ó
- Bromley M
- Brooke H
- Brooks J
- Brooks J
- Brooks S
- Brown A
- Brown A
- Brown A
- Brown CW
- Brown E
- Brown J
- Bruce M
- Brugada R
- Brunton M
- Bryant J
- Buckley C
- Buckley J
- Buckley S
- Bull R
- Bullock E
- Bullock E
- Bunni L
- Burchett C
- Burda D
- Burgoyne A
- Burn I
- Burnett C
- Burnish R
- Burns K
- Burrow A
- Burt K
- Burtenshaw A
- Burton M
- Bustos M
- Butcher D
- Butler A
- Butler J
- Butler S
- Butt F
- Butterworth-Cowin N
- Button H
- Buttriss C
- Cabello A
- Cabral-Ortega L
- Cabrelli L
- Caceres-Agra JJ
- Cagova L
- Calbo E
- Calderón EJ
- Cale E
- Callaghan M
- Callam S
- Calvo CM
- Camacho S
- Campbell A
- Campbell B
- Campbell H
- Campbell R
- Campbell S
- Campos MC
- Campos S
- Camsooksai J
- Candalija AC
- Candon AM
- Capitán CF
- Capozzi L
- Capps N
- Carbonell C
- Cardona-Huerta S
- Cardwell A
- Carioca AAF
- Carmody M
- Carmody S
- Carnahan M
- Carpintero MS
- Carracedo A
- Carracedo A
- Carratto TMT
- Carrera LG
- Carrillo-Avila JA
- Carson G
- Cart C
- Carter A
- Carter D
- Carter E
- Carter J
- Carter M
- Carter S
- Cartlidge D
- Carungcong J
- Carvalho MCC
- Casasnovas C
- Casey M
- Castano L
- Castaño CF
- Castaño JAT
- Castelao JE
- Castillo MA
- Caswell M
- Caterson J
- Cathcart S
- Catlow L
- Cavazza A
- Cave A
- Cawley K
- Cawley K
- Cawthron K
- Cañadas Y
- Ceballos FC
- Cha M
- Chablani M
- Chadwick R
- Chan R
- Chand M
- Chandler B
- Chandna H
- Chapman S
- Charles B
- Charlesworth R
- Charnock R
- Charris HM
- Chaux JG
- Chaves-Santiago WG
- Chechi K
- Cheema Y
- Chen J
- Cherian S
- Chesters K
- Chetam L
- Cheyne C
- Chikowore P
- Childs D
- Chiquillo-Gómez S
- Chisholm C
- Choudhr O
- Choudhury Y
- Chukkambotla S
- Chávez MEQ
- Cid-Lopez MA
- Cienfuegos-Jimenez O
- Cinquina Z
- Clamp S
- Clapham M
- Clarey E
- Claridge H
- Clark A
- Clark A
- Clark M
- Clark M
- Clark R
- Clark R
- Clark S
- Clark S
- Clark V
- Clarke N
- Clarkson M
- Clayton S
- Clement I
- Clements S
- Clohisey S
- Coates C
- Cochrane P
- Cockerill H
- Cockrell M
- Coe R
- Coetzee S
- Coghlan P
- Cohrane C
- Coker D
- Cole J
- Cole J
- Cole S
- Coleman C
- Coleman D
- Coles H
- Colley J
- Colley N
- Collier D
- Collier D
- Collier H
- Collins A
- Collins C
- Collins E
- Collins E
- Collins K
- Collins K
- Collins R
- Collins V
- Collis M
- Combes E
- Conde-Vicente R
- Conejo IP
- Connell J
- Connolly K
- Connor M
- Convery K
- Conyngham J-A
- Cooke GS
- Cookson R
- Cooper J
- Cooper L
- Cooper L
- Corcoran E
- Corcoran K
- Cordero-Lorenzana ML
- Corella D
- Corin C
- Cornell S
- Cornell T
- Corner A
- Corral MA
- Corrales A
- Cortes-Sanchez JL
- Corton M
- Cosgrove D
- Cosier T
- Costa TX
- Cother N
- Coton Z
- Cottam L-J
- Cottle J
- Coulding M
- Coutts A
- Coventry T
- Covernton P
- Cowley A
- Cowley N
- Cowton A
- Cox A
- Coyle J
- Craig H
- Craig J
- Crawley R
- Creagh-Brown B
- Crew A
- Crickmore V
- Cristiano D
- Croft M
- Crowe R
- Crowley M
- Cruz C
- Cruz MS
- Cruz R
- Cruz R
- Csabi P
- Cuerda VM
- Cuesta L
- Cullum L
- Cunha GCR
- Cunningham A
- Cunningham M
- Cupitt J
- Curgenven H
- Currie S
- Cusack R
- Cutler S
- Cutting P
- Cutts S
- Da Gloria EF
- Da Rocha J
- da Silva Filipe A
- da Silva GV
- Daglish J
- Dagutao Z
- Dale K
- Dale S
- Dalmau D
- Dalton C
- Dalton J
- Daly Z
- Dalziel J
- DAmato F
- Dance A
- Daniel A
- Daniel E
- Daniel P
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- Dantas-Komatsu RCS
- Dark P
- Darlington K
- Darnaude MT
- Darnell S
- Das M
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- Daubney E
- Davey M
- David B
- Davidson N
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- Davies R
- Davies S
- Davis C
- Davis J
- Davison C
- Dawson A
- Dawson D
- Day A
- Day N
- de Andrés R
- de Araújo JNG
- De Beger S
- de Bustamante AD
- de Gordoa LO-R
- de Heredia ML
- de Juan C
- De la Cruz Troca J
- de la Horra C
- de la Hoz AB
- De Martino-Rodríguez A
- de Neef M
- De Queiroz JG
- de Quirós FGB
- de Silva T
- de Sousa Alves Neri JL
- Deacon B
- Deacon B
- Dean C
- Dearden J
- DeAth Y
- Debreceni G
- Deery J
- del Campo-Pérez V
- Dela Rosa A
- Delaney J
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- Dell A
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- Dennis C
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- Dexter C
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- Diaz-Caneja CM
- Dickson H
- Dietl B
- Digby B
- Digby S
- Ding L
- Diz-de Almeida S
- Djeugam B
- Doble P
- Dobson E
- Docherty AB
- Dodd A
- Dodds S
- Dolan H
- Domingos P
- Domínguez-Garrido E
- Donaldson A
- Donaldson D
- Donegan C
- Donlon S
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- Donne B
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- Donnison P
- Donohue C
- Dooks E
- Doonan R
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- dos Santos KA
- Douglas K
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- Drake TM
- Drummond A
- Duarte AM
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- Dumas M-E
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- Durie A
- Durrans LJ
- Durrant G
- Duskova M
- Dykes J
- Díaz-Pérez A
- D’Sylva S
- Eapen B
- Earl V
- Eastgate C
- Easthope A
- Easthope A
- Easthope A
- Easton J
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- Edmond I
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- Elhassan M
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- Eltayeb A
- Emblem J
- Enciso-Olivera CO
- English K
- Eros A
- Escudero G
- Esparza-Gordillo J
- España PP
- Estévez JV
- Evans G
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- Farquhar F
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- Faulkner M
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- Fernandez Z
- Fernandez-Caballero L
- Fernandez-Nestosa MJ
- Fernandez-Roman J
- Fernández AM
- Fernández FA
- Fernández R
- Fernández-Cruz A
- Fernández-Robelo U
- Fernández-Rodríguez A
- Fernández-Sampedro M
- Fernández-Sánchez R
- Fernández-Villa T
- Ferrero SF
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- Fuentes CS
- Fumadó V
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- Gagliardi L
- Gago-Domínguez M
- Gales A
- Gallagher B
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- Gallego N
- Gallo JPV
- Galoppo C
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- Garcia-Cerrada C
- Garcia-García J
- García FR
- García I
- García L
- García M
- García MG
- García PM
- García-de-Vicuña A
- García-García I
- García-Ibarbia C
- García-Montero AC
- García-Soidán A
- García-Vázquez E
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- Gnanapragasam P
- Goddard W
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- Gude ET
- Guegel GP
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- Guillen-Navarro E
- Guisado-Vasco P
- Gulati A
- Gumbrill B
- Gummadi M
- Gupta A
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- Gutierrez-Castañeda LD
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- Íñiguez M
- Publication venue
- Springer Nature
- Publication date
- 17/05/2023
- Field of study
Data availability: Downloadable summary data are available through the GenOMICC data site (https://genomicc.org/data). Summary statistics are available, but without the 23andMe summary statistics, except for the 10,000 most significant hits, for which full summary statistics are available. The full GWAS summary statistics for the 23andMe discovery dataset will be made available through 23andMe to qualified researchers under an agreement with 23andMe that protects the privacy of the 23andMe participants. For further information and to apply for access to the data, see the 23andMe website (https://research.23andMe.com/dataset-access/). All individual-level genotype and whole-genome sequencing data (for both academic and commercial uses) can be accessed through the UKRI/HDR UK Outbreak Data Analysis Platform (https://odap.ac.uk). A restricted dataset for a subset of GenOMICC participants is also available through the Genomics England data service. Monocyte RNA-seq data are available under the title ‘Monocyte gene expression data’ within the Oxford University Research Archives (https://doi.org/10.5287/ora-ko7q2nq66). Sequencing data will be made freely available to organizations and researchers to conduct research in accordance with the UK Policy Framework for Health and Social Care Research through a data access agreement. Sequencing data have been deposited at the European Genome–Phenome Archive (EGA), which is hosted by the EBI and the CRG, under accession number EGAS00001007111.Extended data figures and tables are available online at https://www.nature.com/articles/s41586-023-06034-3#Sec21 .Supplementary information is available online at https://www.nature.com/articles/s41586-023-06034-3#Sec22 .Code availability:
Code to calculate the imputation of P values on the basis of SNPs in linkage disequilibrium is available at GitHub (https://github.com/baillielab/GenOMICC_GWAS).Acknowledgements: We thank the members of the Banco Nacional de ADN and the GRA@CE cohort group; and the research participants and employees of 23andMe for making this work possible. A full list of contributors who have provided data that were collated in the HGI project, including previous iterations, is available online (https://www.covid19hg.org/acknowledgements).Change history: 11 July 2023: A Correction to this paper has been published at: https://doi.org/10.1038/s41586-023-06383-z. -- In the version of this article initially published, the name of Ana Margarita Baldión-Elorza, of the SCOURGE Consortium, appeared incorrectly (as Ana María Baldion) and has now been amended in the HTML and PDF versions of the article.Copyright © The Author(s) 2023, Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).GenOMICC was funded by Sepsis Research (the Fiona Elizabeth Agnew Trust), the Intensive Care Society, a Wellcome Trust Senior Research Fellowship (to J.K.B., 223164/Z/21/Z), the Department of Health and Social Care (DHSC), Illumina, LifeArc, the Medical Research Council, UKRI, a BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070 and BBS/E/D/30002275) and UKRI grants MC_PC_20004, MC_PC_19025, MC_PC_1905 and MRNO2995X/1. A.D.B. acknowledges funding from the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z), the Edinburgh Clinical Academic Track (ECAT) programme. This research is supported in part by the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant MC_PC_20029). Laboratory work was funded by a Wellcome Intermediate Clinical Fellowship to B.F. (201488/Z/16/Z). We acknowledge the staff at NHS Digital, Public Health England and the Intensive Care National Audit and Research Centre who provided clinical data on the participants; and the National Institute for Healthcare Research Clinical Research Network (NIHR CRN) and the Chief Scientist’s Office (Scotland), who facilitate recruitment into research studies in NHS hospitals, and to the global ISARIC and InFACT consortia. GenOMICC genotype controls were obtained using UK Biobank Resource under project 788 funded by Roslin Institute Strategic Programme Grants from the BBSRC (BBS/E/D/10002070 and BBS/E/D/30002275) and Health Data Research UK (HDR-9004 and HDR-9003). UK Biobank data were used in the GSMR analyses presented here under project 66982. The UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government, British Heart Foundation and Diabetes UK. The work of L.K. was supported by an RCUK Innovation Fellowship from the National Productivity Investment Fund (MR/R026408/1). J.Y. is supported by the Westlake Education Foundation. SCOURGE is funded by the Instituto de Salud Carlos III (COV20_00622 to A.C., PI20/00876 to C.F.), European Union (ERDF) ‘A way of making Europe’, Fundación Amancio Ortega, Banco de Santander (to A.C.), Cabildo Insular de Tenerife (CGIEU0000219140 ‘Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19’ to C.F.) and Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC20/57 to C.F.). We also acknowledge the contribution of the Centro National de Genotipado (CEGEN) and Centro de Supercomputación de Galicia (CESGA) for funding this project by providing supercomputing infrastructures. A.D.L. is a recipient of fellowships from the National Council for Scientific and Technological Development (CNPq)-Brazil (309173/2019-1 and 201527/2020-0)
A second update on mapping the human genetic architecture of COVID-19
- Author
- Abd Elghafar MS
- Abdel-Aziz M
- Abdelrazik M
- Abdullah MS
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- Afset JE
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- Aguado JM
- Aguilar C
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- Aguilar-Salinas CA
- Aguilera-Albesa S
- Agüero D
- Ahmad HF
- Ahmad N
- Ahmadhaider N
- Ahmed A
- Ahmed C
- Ahram M
- Ai M
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- Pestaña D
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- Sekikawa Y
- Sell C
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- Senner F
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- Shankar-Hari M
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- Shivanathan I
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- Shoko T
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- Shoremekun A
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- Solier A
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- Solligård E
- Solomonson M
- Solomonson M
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- Sonobe K
- Soria JM
- Soriano A
- Souto JC
- Speight A
- Speirs S
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- Spinner CD
- Spivey M
- Springle P
- Sra S
- Sri-Chandana C
- Srikaran S
- St-Cyr J
- Stacey A
- Stagg C
- Stammers K
- Stapleton L
- Stark KJ
- Stead R
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- Szakmany T
- Szentpéteri JL
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- Takahashi M
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- Takeda Y
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- Tamayo E
- Tamayo-Velasco A
- Tampsett R
- Tanaka A
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- Tanck A
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- Tani M
- Tanigawa Y
- Tanino Y
- Taniyama D
- Tanudjaja F
- Taracido-Fernandez JC
- Tardif N
- Tariq A
- Tateishi T
- Tateno H
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- Tauekelova A
- Tauro S
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- Tiembe N
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- Timens W
- Timlick E
- Timpson NJ
- Ting L
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- Tivenan H
- Toapanta D
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- Turney S
- Turtle L
- Turvey SE
- Tusié-Luna T
- Tutt G
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- Twiss S
- Tyl D
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- Tzoulaki I
- Téllez L
- Uchimura Y
- Ueda S
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- Uitterlinden AG
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- Umeda A
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- Vadgama N
- Vadla MS
- Vaida M
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- Valdés PA
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- Valenti L
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- Vallerga CL
- Valsecchi MG
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- Van Heel DA
- Van Heel DA
- Van Koutrick L
- Vandernoot I
- Varghese M
- Vasilevska-Ristovska J
- Vassell K
- Vedage D
- Veerapen K
- Vega J
- Vehreschild MJGT
- Velasco DG
- Velázquez-Cruz R
- Venkatesh H
- Verdugo RA
- Verdugo RA
- Vergasova E
- Verlander M
- Vertue M
- Verula J
- Vigueras-Hernández A
- Vigurs C
- Villa A
- Villalonga JM
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- Virgilio E
- Virginia M-RA
- Vitart V
- Vizcaychipi M
- Vlasschaert C
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- Von Hohenstaufen Puoti KA
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- Vázquez-Pérez JA
- Wacker EM
- Wackett T
- Wadams B
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- Waite AAC
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- Washington NL
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- Wyllie DH
- Wynter I
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- Xue X
- Yagi K
- Yamada M
- Yamada Y
- Yamagata K
- Yamasaki M
- Yang J
- Yaspan B
- Yassen AM
- Yasui Y
- Yates B
- Yatomi M
- Ye C
- Yermakovich D
- Yeung RSM
- Yi X
- Yonekawa A
- Yoo S
- Yoon K
- Yoshida K
- Yoshida S
- Yoshida S
- Yoshida T
- Yoshihara T
- Yoshiya K
- Yoshiyama T
- Young M
- Yue F
- Yun N
- Yáñez CE
- Yáñez Z
- Zainulabid UA
- Zainy T
- Zak A
- Zaki A
- Zamikula J
- Zamudio IPM
- Zanella A
- Zapata-Contreras D
- Zapatamartinez M
- Zarate R
- Zarei N
- Zavaleta DAF
- Zawadzki P
- Zawati MH
- Zborowski AC
- Zeberg H
- Zechner M
- Zhang Q
- Zhao X
- Zheng C
- Zheng T
- Zhlawi HJ
- Zhlawi MWJ
- Zholdybayeva E
- Zhou W
- Zhu W
- Zitter L
- Zoller H
- Zongo O
- Zorloni C
- Zuñiga-Pacheco P
- Zárate RN
- Zúñiga-Ramos J
- Álvarez BG
- Ávila-Arcos MA
- Ávila-Arcos MC
- Özer O
- Überla K
- Þorsteinsdóttir U
- Publication venue
- Nature Research
- Publication date
- 21/06/2023
- Field of study