12 research outputs found
Whole-genome sequencing reveals host factors underlying critical COVID-19
- Author
- Abd Elghafar M.S.
- Abdel-Aziz M.
- Abdelrazik M.
- Abdollahi H.
- Abdullah T.
- Abecasis G.R.
- Abecasis G.R.
- Abedalthagafi M.
- Abel L.
- Abernathy C.
- Abraheem A.
- Abul-Husn N.S.
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- Trivedi B.
- Trodd D.
- Trogstad L.-I.S.
- Trotman S.
- Trotta T.
- Trower H.
- Truman N.
- Trumper E.
- Tsao P.
- Tselios C.
- Tsinaslanidis G.
- Tsuo K.
- Tucci A.
- Tuckey V.
- Tully R.
- Tumbarello M.
- Turki S.
- Turley P.
- Turnbull A.
- Turner K.
- Turner L.
- Turner P.
- Turner V.
- Turner-Bone I.
- Turney S.
- Turtle L.
- Tutton R.
- Twiss S.
- Tyl D.
- Tyler A.
- Uitterlinden A.G.
- Underwood S.J.
- Vaghi M.
- Vaida M.
- Valente S.
- Valentine J.
- Valentino F.
- van Blokland I.
- van Heel D.A.
- van Koutrik L.
- Varghese M.
- Vecchia M.
- Vedage D.
- Veerapen K.
- Venkatesh H.
- Venn L.D.
- Venturelli S.
- Vergori A.
- Verlander M.
- Verma A.
- Verma A.
- Verma S.S.
- Vertue M.
- Verula J.
- Verzuri A.
- Vigurs C.
- Villalonga J.M.
- Vincent R.
- Vincenti A.
- Virgilio E.
- Vitart V.
- Vizcaychipi M.P.
- Vochin A.
- Voide C.
- von Frenckell C.
- von Hohenstaufen K.A.
- Vonk J.M.
- Vulesevic B.
- Vuylsteke A.
- Wackett T.
- Wadams B.
- Waddington N.
- Wagstaff V.
- Wain L.V.
- Waite A.A.C.
- Wakefield P.
- Wakinshaw F.
- Waldron J.
- Walker D.
- Walker R.
- Walker S.
- Walker S.
- Walker S.
- Wall A.
- Walsh T.
- Walsh T.
- Walters R.K.
- Walton O.
- Wang B.
- Wang J.
- Wang X.
- Wanying Z.
- Ward G.
- Ward L.
- Ward M.
- Warden S.
- Warmerdam R.
- Warren D.
- Wassall H.
- Wasson C.
- Watkins C.
- Watson E.
- Watson G.
- Watson J.
- Watters M.
- Waugh V.
- Weaver J.
- Webster A.
- Webster D.
- Webster K.
- Wei S.
- Weiss S.T.
- Weldon C.H.
- Wells C.
- Welters I.D.
- Weston H.
- Whileman A.
- Whitbread J.
- White D.
- White I.
- White K.
- White M.
- White N.
- White N.
- Whiteley S.
- Whiteside J.
- Whittle H.
- Whitton C.
- Whyte C.
- Wicks S.J.
- Wilby E.
- Wilcox L.
- Wilcox R.
- Wild H.
- Wild L.
- Wild L.
- Wilding L.
- Wiles M.
- Wilkins J.
- Wilkinson A.
- Wilkinson B.
- Willer C.
- Williams A.
- Williams A.
- Williams A.
- Williams A.T.
- Williams D.
- Williams E.
- Williams F.
- Williams G.
- Williams H.
- Williams K.
- Williams M.
- Williams P.
- Williams S.
- Williams T.
- Willis C.
- Willis H.
- Wills M.
- Willson J.
- Wilson A.
- Wilson D.J.
- Wilson J.
- Wilson J.F.
- Wilson J.F.
- Winnard S.
- Winter-Goodwin B.
- Wolf-Roberts R.
- Wolford B.
- Wong J.
- Wood D.
- Wood H.-L.
- Wood S.
- Wood T.
- Woodford C.
- Woodruff M.
- Woods L.
- Woodyatt W.
- Woolley A.E.
- Worner R.
- Worsley L.
- Wray G.
- Wren L.
- Wrey Brown C.
- Wright D.
- Wright J.
- Wright M.
- Wrobel N.
- Wu Y.
- Wulandari R.
- Wyllie D.H.
- Wynter I.
- Xavier K.
- Xue X.
- Yadav A.
- Yang J.
- Yassen A.M.
- Yates B.
- Ye C.
- Yun N.
- Zainy T.
- Zak A.
- Zaki A.
- Zamikula J.
- Zanella I.
- Zborowski A.C.
- Zeberg H.
- Zechner M.
- Zechner M.
- Zguro K.
- Zhang M.
- Zhao J.H.
- Zheng C.
- Zhou W.
- Zitter L.
- Zlatopolsky M.
- Zongo O.
- Zucchi P.
- Zyndorf M.
- Zöllner S.
- Åsvold B.O.
- Publication venue
- Springer Science and Business Media LLC
- Publication date
- 07/07/2022
- Field of study
Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease
Exploration of the impact of stereochemistry on the identification of the novel translocator protein PET imaging agent [18F]GE-180
- Author
- Alan Clarke
- Andrew M.A. Black
- Astri Rogstad
- Casellas
- Chauveau
- Chen
- Ching
- Clare Durrant
- Damont
- Dimitrios Mantzilas
- Freedman
- Imtiaz Khan
- Inger Oulie
- Ingvil Gausemel
- Kam
- Kuhnast
- Le Fur
- McAfee
- McEnery
- Miyoshi
- Morisson-Iveson
- Nguyen
- O'Shea
- Papadopoulos
- Papadopoulos
- Paul A. Jones
- Pike
- Rupprecht
- Scarf
- Slovakova
- Taylor
- Venneti
- Wadsworth
- Wadsworth
- Wai-Fung Chau
- William Trigg
- Publication venue
- 'Elsevier BV'
- Publication date
- Field of study
How climate and vegetation type influence evapotranspiration and water use efficiency in Canadian forest, peatland and grassland ecosystems
- Author
- Amiro B.D. (Brian D.)
- Arain M.A. (M. Altaf)
- Barr A.G. (Alan G.)
- Black T.A. (T. Andrew)
- Bourque C.P.-A. (Charles P.-A.)
- Brümmer C. (Christian)
- Chen B. (Baozhang)
- Coursolle C. (Carole)
- Dunn A.L. (Allison L.)
- Flanagan L.B. (Lawrence B.)
- Grant N.J. (Nicholas J.)
- Humphreys E. (Elyn)
- Jassal R.S. (Rachhpal S.)
- Lafleur P.M. (Peter M.)
- Margolis H.A. (Hank A.)
- McCaughey J.H. (J. Harry)
- Nesic Z. (Zoran)
- Spittlehouse D.L. (David L.)
- Wofsy S.C. (Steven C.)
- Publication venue
- 'Elsevier BV'
- Publication date
- 15/02/2012
- Field of study
Genetic correlation between amyotrophic lateral sclerosis and schizophrenia
- Author
- Abdulla Susanne
- Adolfsson Rolf
- Agartz Ingrid
- Agerbo Esben
- Al-Chalabi Ammar
- Albus M.
- Alexander M.
- Amin Farooq
- Amouyel Philippe
- Andersen P.M.
- Andreassen Ole A.
- Andres Christian R.
- Anthony O'Neill F.
- Arcuti S.
- Bacanu S.A.
- Basak Nazli
- Bauer Denis
- Begemann M.
- Beghi E.
- Belliveau R.A.
- Bene J.
- Bensimon Gilbert
- Bergen Sarah E.
- Bertolin C.
- Bevilacqua E.
- Bigdeli Tim B
- Black D.W.
- Blackwood Douglas H. R.
- Blagojevic-Radivojkov Milena
- Blair I.
- Bo R.D.
- Bradley Daniel G.
- Bramon Elvira
- Breen G.
- Brice Alexis
- Brown R. H.
- Bruggeman R.
- Brunetti M.
- Buccola N.G.
- Buckner R.L.
- Bulik-Sullivan B.
- Buxbaum Joseph D.
- Byerley W.
- Børglum Anders D.
- Cahn Wiepke
- Cai G.
- Calvo A.
- Campion D.
- Cantor R.M.
- Capozzo Rosa
- Carr Vaughan J
- Carrera N.
- Casale F.
- Catts S.V.
- Cereda C.
- Chambert K.D.
- Chan R.C.K.
- Chan R.Y.L.
- Chandran Siddharthan
- Chen E.Y.H.
- Cheng W.
- Cheung E.F.C.
- Chio A.
- Chong S.A.
- Cichon Sven
- Cloninger C.R.
- Cohen D.
- Cohen N.
- Collier D.A.
- Colville Shuna
- Comi G.P.
- Corcia P.
- Cormican P.
- Corvin A.
- Craddock N.
- Crowley J.J.
- Curtis Charles
- Curtis D.
- D'Alfonso S.
- Daly Mark J.
- Damme P.V.
- Dartigues Jean- François
- Darvasi Ariel
- Davidson M.
- Davis K.L.
- de Carvalho Mamede
- De Haan L.
- de Visser Marianne
- Degenhardt F.
- Dekker Annelot M.
- Demontis D.
- Diekstra Frank P.
- Dikeos D.
- Dinan T.
- Djurovic S.
- Domenici Enrico
- Donohoe G.
- Drapeau E.
- Drepper Carsten
- Duan J.
- Dudbridge F.
- Durmishi N.
- Durr Alexandra
- Eftimov Filip
- Ehrenreich Hannelore
- Eichhammer P.
- Elman Lauren B.
- Eriksson J.
- Es M.A.V.
- Escott-Price Valentina
- Esko Tõnu
- Essioux L.
- Estrada Karol
- Fanous A.H.
- Farh K.H.
- Farrell M.S.
- Favero J.D.
- Filosto M.
- Fogh Isabella
- Frank J.
- Franke Andre
- Franke L.
- Fratta Pietro
- Freedman R.
- Freimer N.B.
- Friedl M.
- Friedman J.I.
- Fromer M.
- Gejman Pablo V.
- Gellera C.
- Genovese G.
- Georgieva L.
- Giegling I.
- Gil Michael
- Giusti-Rodrýguez P.
- Glass J.
- Godard S.
- Goldstein Jacqueline I.
- Golimbet V.
- Gopal S.
- Goris An
- Gratten J.
- Gurling Hugh
- Hammer C.
- Hamshere M.L.
- Hansen M.
- Hansen T.
- Hardiman Orla
- Hardy John
- Haroutunian V.
- Hartmann A.M.
- Henskens F.A.
- Herms S.
- Hirschhorn J.N.
- Hoffmann P.
- Hofman A.
- Hofman Albert
- Hollegaard M.V.
- Holmans P.A.
- Hong Lee S.
- Hougaard D.M.
- Huang H.
- Hultman Christina M.
- Ikeda M.
- Iwata Nakao
- Jablensky Assen V.
- Joa I.
- Jones Ashley R.
- Jonsson Erik G.
- Julia Antonio
- Kahler A.K.
- Kahlke Tim
- Kahn René S.
- Kalaydjieva L.
- Karachanak-Yankova S.
- Karjalainen J.
- Kavanagh D.
- Keller M.C.
- Kendler Kenneth S.
- Kennedy J.L.
- Khrunin A.
- Kiernan Matthew C.
- Kim Y.
- Kirov George
- Klovins J.
- Knight Jo
- Knowles J.A.
- Konte B.
- Kucinskas V.
- Kucinskiene Z.A.
- Kuzelova-Ptackova H.
- Landers John E
- Landwehrmeyer Georg Bernhard
- Laurent C.
- Lee J.
- Lee P.
- Legge S.E.
- Lencz Todd
- Lerer B.
- Levinson Douglas F.
- Lewis C.M.
- Li M.
- Li Qingqin S.
- Li T.
- Liang K.Y.
- Lichtner Peter
- Lieb Wolfgang
- Lieberman J.
- Limborska S.
- Lin Kuang
- Liu Jianjun
- Logroscino G.
- Lomen-Hoerth Catherine
- Lonnqvist J.
- Loughland C.M.
- Lubinski J.
- Ludolph A.C.
- Lunetta C.
- Luykx Jurjen J.
- MacEk M.
- Magnusson P.K.E.
- Maher B.S.
- Maier W.
- Malaspina Andrea
- Malhotra Anil K.
- Mallet J.
- Marsal Sara
- Mattheisen M.
- Mattingsdal M.
- Maurel Cindy
- Mazzini L.
- McCarley R.W.
- McCarroll Steven A.
- McCluskey Leo
- McDonald C.
- McIntosh A.M.
- McLaughlin Russell L.
- McQuillin Andrew
- Meier S.
- Meijer C.J.
- Meininger Vincent
- Meitinger Thomas
- Melegh B.
- Melle I.
- Mesholam-Gately R.I.
- Metspalu A.
- Meyer Thomas
- Michie P.T.
- Milani L.
- Milanova V.
- Millecamps Stéphanie
- Moglia C.
- Mokrab Y.
- Mora Jesús S.
- Moran Jennifer
- Morris D.W.
- Morrison Karen E.
- Mors O.
- Mortensen Preben Bo
- Mowry Bryan J.
- Muller-Myhsok B.
- Murphy K.C.
- Murray R.M.
- Myin-Germeys I.
- Neale B.M.
- Nelis M.
- Nenadic I.
- Nertney D.A.
- Nestadt G.
- Nicholson Garth A.
- Nicodemus K.K.
- Nigel Leigh P.
- Nikitina-Zake L.
- Nisenbaum L.
- Nordin A.
- Nothen Markus M.
- O'Brien Margaret
- O'Callaghan E.
- O'Donovan Michael C.
- O'Dushlaine C.
- Oh S.Y.
- Olincy A.
- Olsen L.
- Ophoff Roel A.
- Orrell Richard W.
- Owen Michael J.
- Padovani A.
- Palotie Aaron
- Pamphlett Roger
- Pansarasa O.
- Pantelis C.
- Papadimitriou G.N.
- Papiol S.
- Parkhomenko E.
- Pasterkamp R.J.
- Pato Carlos N.
- Pato M.T.
- Paunio T.
- Payan Christine A. M.
- Pejovic-Milovancevic M.
- Penco S.
- Pensato V.
- Perkins D.O.
- Pers T.H.
- Petri Susanne
- Petryshen Tracey L.
- Pietilainen O.
- Pimm J.
- Pinto Susana
- Pittman Alan
- Pocklington A.J.
- Polak Meraida
- Posthuma Danielle
- Powell J.
- Price A.
- Pulit Sara L.
- Pulver A.E.
- Pupillo E.
- Purcell S.M.
- Quested D.
- Rasmussen H.B.
- Ratti A.
- Reichenberg A.
- Reimers M.A.
- Richards A.L.
- Rietschel Marcella
- Riley Brien Patrick
- Ripke S.
- Riva N.
- Rivadeneira Fernando
- Robberecht W.
- Roffman J.L.
- Rojas-Garcia Ricard
- Roussos P.
- Rowe Dominic B.
- Ruderfer D.M.
- Rujescu Dan
- Saker-Delye Safa
- Salachas François
- Salomaa V.
- Sanders A.R.
- Schall U.
- Schijven Dick
- Schubert C.R.
- Schulze T.G.
- Schwab S.G.
- Scolnick E.M.
- Scott Stroup T.
- Scott R.J.
- Seidman L.J.
- Sendtner Michael
- Sham Pak C.
- Shatunov Aleksey
- Shaw Christopher
- Shaw Pamela
- Shi J.
- Sidle Katie
- Sigurdsson E.
- Silagadze T.
- Silani V.
- Silverman J.M.
- Sim K.
- Sklar Pamela
- Slominsky P.
- Smith B.N.
- Smoller J.W.
- So H.C.
- Soraru G.
- Spencer C.C.A.
- Sproviero William
- St Clair David
- Stah E.A.
- Stefansson H.
- Stefánsson Kári
- Steinberg S.
- Stogmann E.
- Straub R.E.
- Strengman E.
- Strohmaier J.
- Subramaniam M.
- Sullivan Patrick F.
- Suvisaari J.
- Svrakic D.M.
- Swingler Robert
- Szatkiewicz J.P.
- Söderman E.
- Thirumalai S.
- Ticozzi Nicola
- Tiloca C.
- Tittmann Lukas
- Toncheva D.
- Tortelli R.
- Tosato S.
- Trojanowski John Q.
- Tzourio Christophe
- Uitterlinden André G.
- Universitat Autònoma de Barcelona
- van Deerlin Vivianna M.
- van den Berg Leonard H.
- van der kooi Anneke Jelly
- van der Spek Rick A.A.
- van Doormaal Perry TC.
- Van Eijk Kristel R.
- van Rheenen Wouter
- Vanos J.
- Veijola J.
- Veldink Jan
- Visscher PM
- Vourc'H P.
- Waddington J.
- Walsh D.
- Walters J.T.R.
- Wang D.
- Wang Q.
- Webb B.T.
- Weber Markus
- Weinberger Daniel R.
- Weiser Mark
- Weishaupt J.H.
- Wendland Jens
- Werge Thomas
- Wiedau-Pazos Martina
- Wildenauer Dieter B.
- Williams Kelly
- Williams Nigel M.
- Williams Stephanie
- Witt Stephanie H.
- Wolen Aaron R.
- Wong Emily H. M.
- Wood Nicholas
- Wormley Brandon K.
- Wray Naomi R.
- Xi Hualin S.
- Zai Clement C.
- Zecca C.
- Zheng Xuebin
- Zimprich Fritz
- Publication venue
- Publication date
- 01/01/2017
- Field of study
We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P=1 × 10) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P=8.4 × 10). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies
A model-data comparison of gross primary productivity: Results from the north American carbon program site synthesis
- Author
- Anderson R. (Ryan)
- Arain M.A. (M. Altaf)
- Baker I. (Ian)
- Barr A. (Alan)
- Black T.A. (T. Andrew)
- Bolstad P. (Paul)
- Chen J. (Jiquan)
- Chen J.M. (Jing M.)
- Curtis P.S. (Peter S.)
- Davis K.J. (Kenneth J.)
- Desai A.R. (Ankur R.)
- Dietze M. (Michael)
- Dimitrov D. (Dimitre)
- Dragoni D. (Danilo)
- Gough C. (Christopher)
- Grant R.F. (Robert F.)
- Gu L. (Lianhong)
- Hilton T.W. (Timothy W.)
- Hollinger D.Y. (David Y.)
- Humphreys E. (Elyn)
- Jain A. (Atul)
- Kucharik C. (Chris)
- Law B. (Beverly)
- Liu S. (Shuguang)
- Lokipitiya E. (Erandathie)
- Margolis H.A. (Hank A.)
- Matamala R. (Roser)
- McCaughey J.H. (J. Harry)
- Monson R. (Russ)
- Munger J.W. (J. William)
- Oechel W. (Walter)
- Peng C. (Changhui)
- Poulter B. (Benjamin)
- Price D.T. (David T.)
- Raczka B.M. (Brett M.)
- Ricciuto D. (Dan)
- Richardson A.D. (Andrew D.)
- Riley W.J. (William J.)
- Roulet N. (Nigel)
- Sahoo A. (Alok)
- Schaefer K. (Kevin)
- Schwalm C.R. (Christopher R.)
- Thornton P. (Peter)
- Tian H. (Hanqin)
- Tonitto C. (Christina)
- Torn M. (Margaret)
- Vargas R. (Rodrigo)
- Verbeeck H. (Hans)
- Weng E. (Ensheng)
- Williams C. (Chris)
- Zhou X. (Xiaolu)
- Publication venue
- 'American Geophysical Union (AGU)'
- Publication date
- 01/09/2012
- Field of study
Advances in meningioma therapy
- Author
- A. Keller
- A. Maillo
- A. Perry
- A. Wigertz
- A.E. Elia
- A.E. Harris
- Andrew D. Norden
- B. Custer
- B.J. Goldsmith
- B.S. Schoenberg
- C. Bruns
- C. Marosi
- C. Muhr
- C.M. Hansson
- C.O. Hanemann
- D. Pasquier
- D. Simpson
- E. Gay
- E.A. Lusis
- E.B. Claus
- E.B. Claus
- G.S. Baia
- H.B. Newton
- I.E. McCutcheon
- J. Debus
- J. Jaaskelainen
- J. Provias
- J.S. Smith
- J.W. Goodwin
- Jan Drappatz
- K. Lamszus
- K. Lamszus
- K. Striedinger
- K. Wozniak
- L. Bethke
- L. Klaeboe
- L. Rogers
- L.A. Zeidman
- L.K. Goyal
- M. Aarhus
- M. Johnson
- M. Nakamura
- M. Simon
- M.A. Gerber
- M.C. Chamberlain
- M.C. Chamberlain
- M.C. Chamberlain
- M.C. Chamberlain
- M.C. Chamberlain
- M.H. Ruttledge
- N. Krayenbuhl
- P. Kan
- P. Rajaraman
- P. Robles de
- P.M. Black
- P.Y. Wen
- Patrick Y. Wen
- R. Deboer
- R. Gazzeri
- R. Ketter
- R. Ketter
- R.C. Torres
- R.S. Kerbel
- S. Arena
- S. Blitshteyn
- S. Milker-Zabel
- S.G. Ojemann
- S.L. Stafford
- S.M. Grunberg
- S.Y. Yang
- T. Crombet
- T. Kaley
- T.W. Dziuk
- V. Barresi
- V. Gupta
- V. Martinez-Glez
- W. Krupp
- W.D. Johnson
- W.K. Pfisterer
- W.M. Drake
- Y. Morofuji
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Copy number variation in obsessive-compulsive disorder and tourette syndrome: A cross-disorder study
- Author
- Arnold P.D. (Paul)
- Barr C.L. (Cathy)
- Bellodi L. (Laura)
- Benarroch F. (Fortu)
- Bienvenu O.J. (Oscar)
- Black D.W. (Donald)
- Bloch J. (Jocelyne)
- Brentani H. (Helena)
- Bruun R.D. (Ruth)
- Budman C.L. (Cathy)
- Camarena B. (Beatriz)
- Cappi C. (Carolina)
- Cath D. (Daniëlle)
- Cavallini M.C. (Maria)
- Chouinard S.
- Cook E.H. (Edwin)
- Coric V. (Vladimir)
- Cox N.J. (Nancy)
- Cullen C.
- Davis L.K. (Lea)
- Delorme R. (Richard)
- Denys D.A.J.P. (Damiaan)
- Derks E.M. (Eske)
- Dion Y. (Yves)
- Eapen C.E. (Chundamannil Eapen)
- Evans P.
- Fagerness J. (Jesen)
- Falkai P. (Peter)
- Fernandez T.V. (Thomas)
- Freimer N.B. (Nelson)
- Gallagher P. (Patience)
- Garrido H. (Helena)
- Geller D. (Daniel)
- Gerber G. (Gloria)
- Grabe H.J. (Hans Jörgen)
- Grados M. (Marco)
- Greenberg B.D. (Benjamin)
- Gross-Tsur V. (Varda)
- Grünblatt E. (Edna)
- Haddad S. (Stephen)
- Hanna G.L. (Gregory)
- Heiman M.L. (Mark)
- Hemmings S.M.J. (Sian)
- Herrera L.D. (Luis)
- Heutink P. (Peter)
- Hounie A.G. (Ana)
- Illmann C. (Cornelia)
- Jankovic J. (Joseph)
- Jenike M.A. (Michael)
- Kennedy J.L.
- King R.A.
- Kirby A. (Andrew)
- Knowles J.A. (James A)
- Kurlan R.
- Lanzagorta N. (Nuria)
- Leboyer M. (Marion)
- Leckman J.F.
- Lennertz L. (Leonhard)
- Li B. (Bingbin)
- Lochner C. (Christine)
- Lowe T.L. (Thomas)
- Lyon H.N. (Helen)
- MacCiardi F. (Fabio)
- Maier W. (Wolfgang)
- Marshall C.R. (Christian)
- Mathews C.
- McCracken J.T. (James)
- McGrath L.M.
- McMahon W.M. (William)
- Miguel E.C. (Euripedes)
- Moessner R. (Rainald)
- Murphy D.L. (Dennis)
- Naarden A.L. (Allan)
- Neale B.M. (Benjamin)
- Nestadt G. (Gerald)
- Nicolini H. (Humberto)
- Nurmi E. (Erika)
- O'Dushlaine C. (Colm)
- Oostra B.A. (Ben)
- Osiecki L. (Lisa)
- Pakstis A.J.
- Pato C. (Carlos)
- Pato C. (Carlos)
- Pauls D.L. (David)
- Petryshen T.L. (Tracey)
- Piacentini J. (John)
- Pittenger C. (Christopher)
- Pollak M.N. (Michael)
- Posthuma D. (Danielle)
- Reus V.I. (Victor)
- Richter M.A. (Margaret)
- Riddle M. (Mark)
- Robertson M.M.
- Rosenberg D. (David)
- Rosário M.C. (Maria)
- Rouleau G.A.
- Ruhrmann S. (Stephan)
- Ruiz-Linares A. (Andres)
- Sampaio A.S. (Aline)
- Samuels J. (Jonathan)
- Sandor P. (Paul)
- Scharf J.M.
- Scherer S.W. (Stephen)
- Schroeder F.A. (Frederick)
- Sheppard B. (Brooke)
- Shugart Y.Y.
- Singer H.S. (Harvey)
- Smit J.H. (Jan)
- Stein D.J. (Dan)
- Stewart S.E.
- Thiruvahindrapuram B. (Bhooma)
- Tischfield J.A. (Jay)
- Vallada H. (Homero)
- Veenstra-Vanderweele J. (Jeremy)
- Wagner M. (Michael)
- Walitza S. (Susanne)
- Wang K. (Kai)
- Wang Y. (Ying)
- Wendland A. (Annika)
- Wolf A. (Anneke) de
- Yu D. (D.)
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2014
- Field of study
Objective Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date. Method The primary analyses used a cross-disorder design for 2,699 case patients (1,613 ascertained for OCD, 1,086 ascertained for TS) and 1,789 controls. Parental data facilitated a de novo analysis in 348 OCD trios. Results Although no global CNV burden was detected in the cross-disorder analysis or in secondary, disease-specific analyses, there was a 3.3-fold increased burden of large deletions previously associated with other neurodevelopmental disorders (p =.09). Half of these neurodevelopmental deletions were located in a single locus, 16p13.11 (5 case patient deletions: 0 control deletions, p =.08 in the current study, p =.025 compared to published controls). Three 16p13.11 deletions were confirmed de novo, providing further support for the etiological significance of this region. The overall OCD de novo rate was 1.4%, which is intermediate between published rates in controls (0.7%) and in individuals with autism or schizophrenia (2-4%). Conclusion Several converging lines of evidence implicate 16p13.11 deletions in OCD, with weaker evidence for a role in TS. The trend toward increased overall neurodevelopmental CNV burden in TS and OCD suggests that deletions previously associated with other neurodevelopmental disorders may also contribute to these phenotypes
Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity
- Author
- Adamo M. (Marco)
- Afzal U. (Uzma)
- Ala-Korpela M. (Mika)
- Albetti B. (Benedetta)
- Ammerpohl O. (Ole)
- Apperley J. (Jane)
- Batterham R.L.
- Beekman M. (Marian)
- Bell J.T. (Jordana T.)
- Bertazzi P.A. (Pier Alberto)
- Black S.L. (S. Lucas)
- Blancher C. (Christine)
- Bollati V. (Valentina)
- Bonder M.J. (Marc)
- Brosch M. (Mario)
- Carstensen-Kirberg M. (Maren)
- Chambers J.C. (John C.)
- Craen A.J. (Anton) de
- Dehghan A. (Abbas)
- Deloukas P. (Panos)
- Drong A. (Alexander)
- Duijn C.M. (Cornelia) van
- Elkalaawy M. (Mohamed)
- Elliott P. (Paul)
- Fiorito G. (Giovanni)
- Fischer K. (Krista)
- Franco O.H. (Oscar)
- Franke L. (Lude)
- Gaunt T.R. (Tom)
- Gieger C. (Christian)
- Grallert H. (Harald)
- Guarrera S. (Simonetta)
- Hampe J. (Jochen)
- Harst P. (Pim) van der
- Hashemi M. (Majid)
- Heijmans B.T. (Bastiaan T.)
- Herder C. (Christian)
- Hofman A. (Albert)
- Illig T. (Thomas)
- Isaacs A.J. (Aaron)
- Jarvelin M.-R. (Marjo-Riitta)
- Jenkinson A. (Andrew)
- Jha S. (Sujeet)
- Kasela S. (Silva)
- Kato N. (Norihiro)
- Kooner J.S. (Jaspal S.)
- Kriebel J. (Jennifer)
- Krogh V. (Vittorio)
- Kunze S. (Sonja)
- Laffan M. (Michael)
- Lehne B. (Benjamin)
- Lindgren C.M. (Cecilia M.)
- Loh M. (Marie)
- Lusignan S. (Simon) de
- Matullo G.
- McCarthy M.I. (Mark)
- Meisinger C. (Christa)
- Meitinger T. (Thomas)
- Meurs J.B.J. (Joyce) van
- Milani L. (Lili)
- Mok Z.Y. (Zuan Yu)
- Motta V. (Valeria)
- Ng H.K. (Hong Kiat)
- Nikolakopoulou Z. (Zacharoula)
- Nteliopoulos G. (Georgios)
- Panico S. (Salvatore)
- Pervjakova N. (Natalia)
- Peters A. (Annette)
- Prokisch H. (Holger)
- Rathmann W. (Wolfgang)
- Relton C.L. (Caroline)
- Richmond R.C. (Rebecca C.)
- Ried J.S. (Janina S.)
- Roden M. (Michael)
- Rota F. (Federica)
- Rozario M.A. (Michelle Ann)
- Sandling J.K. (Johanna)
- Schafmayer C. (Clemens)
- Schramm K. (Katharina)
- Scott J. (James)
- Scott W.R. (William R.)
- Siebert R. (Reiner)
- Slagboom P.E. (Eline)
- Smith A.V. (Davey)
- Soininen P. (Pasi)
- Soong R. (Richie)
- Spector T.D. (Timothy)
- Stolk L. (Lisette)
- Strauch K. (Konstantin)
- Tai E.S. (Shyong)
- Tan S. (Sili)
- Tarantini L. (Letizia)
- Thorand B. (Barbara)
- Tigchelaar E.F. (Ettje F.)
- Tsai P.-C. (Pei-Chien)
- Tumino R. (Rosario)
- Uitterlinden A.G. (André)
- Vineis P. (Paolo)
- Wahl S. (Simone)
- Waldenberger M. (Melanie)
- Wickremasinghe A.R. (Ananda)
- Wijmenga C. (Cisca)
- Yang T.-P. (Tsun-Po)
- Yang Y. (Youwen)
- Yuan W. (Wei)
- Zhang W. (Weihua)
- Zhernakova A. (Alexandra)
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 05/01/2017
- Field of study
Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type 2 diabetes, cardiovascular disease and related metabolic and inflammatory disturbances. Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation, a key regulator of gene expression and molecular phenotype. Here we use epigenome-wide association to show that body mass index (BMI; a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci with P < 1 × 10 -7, range P = 9.2 × 10 -8 to 6.0 × 10 -46; n = 10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find that methylation loci are enriched for functional genomic features in multiple tissues (P < 0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci (P < 9.0 × 10 -6, range P = 5.5 × 10 -6 to 6.1 × 10 -35, n = 1,785 samples). The methylation loci identify genes involved in lipid and lipoprotein metabolism, substrate transport and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future development of type 2 diabetes (relative risk per 1 standard deviation increase in methylation risk score: 2.3 (2.07-2.56); P = 1.1 × 10 -54). Our results provide new insights into the biologic pathways influen
Feminist comparative policy: A new field of study
- Author
- Abels G.
- Abrar S.
- Acker J.
- Almond G.A.
- Andrew C.
- Ashford D.E.
- Baldcock C.V.
- Banaszak L.A.
- Banaszak L.A.
- Bashevkin S.
- Bashevkin S.
- Beckman P.R.
- Beckwith K.
- Black N.
- Black N.
- Bock G.
- Bock G.
- Boneparth E.
- Borrelli M.A.
- Buckley M.
- Bussemaker J.
- Bystydzienski J.M.
- Caporaso J.A.
- Caroll SJ.
- Chow E.N.
- Cockburn C.
- Collier David
- Conway J.
- Cook A.
- Cossman B.
- Costain A.N.
- Dahlerup D.
- Daniels C.R.
- Davis R.H.
- Diamond I.
- Drew E.
- Duchen C.
- Duerst-Lahti G.
- Edelman M.
- Eisenstein H.
- Elman A.R.
- Elman A.R.
- Epstein C.F.
- Feick J.
- Ferguson K.E.
- Ferree M.M.
- Field M.J.
- Franzway S.
- Gardiner F.
- Gelb J.
- Gelb J.
- Githens M.
- Githens M.
- Gordon L.
- Gregory J.
- Gustafsson G.
- Haavio-Mannila E.
- Hallett C.
- Harrop M.
- Hart V.
- Heatlinger A.
- Heidenheimer A.J.
- Hernes H.M.
- Hobson B
- Hoskyns C.
- Inglehart R.
- Jenson J.
- Jenson J.
- Jones K.B.
- Kahn P.
- Kammerman S.B.
- Kammerman S.B.
- Kaplan G.
- Katzenstein M.
- Kelly R.M.
- Kingdon J.
- Knesi H.
- Kornbluh F.A.
- Lane R.
- Lawlor E.F.
- Leira A.
- Lewis J.
- Lewis J.
- Lewis J.
- Liebfried S.
- Lijphart A.
- Lijphart A.
- Lipman-Bluman J.
- Lovenduski J.
- Lovenduski J.
- Lovenduski J.
- Lovenduski J.
- Lovenduski J.
- Lovenduski J.
- Lovenduski J.
- Lowi T.
- Lycklama a Nijeholt G.
- Mazur A.
- Mazur A.
- Mazur A.
- McCool D.C.
- Meehan E.
- Meehan E.
- Meehan E.
- Meehan E.
- Nelson B.J.
- Nelson B.J.
- Nettl J.P.
- Norris P.
- Orloff A.S.
- Ostner I.
- Outshoorn J.
- Pateman C.
- Phillips A.
- Phillips A.
- Pitkin H.F.
- Pringle R.
- Randall V.
- Randall V.
- Randall V.
- Ratner Steinberg R.
- Rees T.
- Roth P.
- Ruggie M.
- Safilios-Rothschild C.
- Sainsbury D.
- Sainsbury D.
- Sainsbury D.
- Sapiro V.
- Sassoon A.S.
- Savage M.
- Sawer M.
- Schattschneider E.E.
- Scott J.
- Scott J.W.
- Siltanen J.
- Silverberg H.
- Skocpol T.
- Staudt K.
- Staudt K.A.
- Stetson D.M.
- Stetson D.M.
- Stetson D.M.
- Stetson D.M.
- Tarrow S.
- Thomas S.
- Threlfall M.
- Tolleson R.S.
- Vallance E.
- Watson S.
- Wiarda H.
- Wiarda H.J.
- Wieringa S.
- Yohalem A.M.
- Publication venue
- 'Wiley'
- Publication date
- Field of study
Whole-genome sequencing reveals host factors underlying critical COVID-19
- Author
- Abd Elghafar Mohamed S.
- Abdel-Aziz Mahmoud
- Abdelrazik Marwa
- Abdollahi Hamed
- Abdullah T.
- Abecasis Goncalo
- Abedalthagafi M.
- Abel Lynn
- Abernathy C.
- Abraheem Azmeralde
- Abul-Husn Noura S.
- Acquilini D.
- Adams C.
- Adams Emma L.
- Adams K.
- Adamsara Alireza
- Adanini Olurenke
- Adeleye O.
- Adra D.
- Afilalo J.
- Afilalo M.
- Afolabi D.
- Afrasiabi Z.
- Agasou A.
- Agrawal Shruti
- Agüero D.
- Ahmad N.
- Ahmadi Saeideh
- Ahmed A.
- Ahmed Cecilia
- Akeroyd L.
- Akhtar M.N.
- Akinkugbe O.
- Aksentijevich Alexandra
- 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 Afshar Etemadi
- Alexander Peter.
- Alfonso J.
- Alghamdi B.
- Alghamdi J.
- Ali A.
- Ali Altaf
- Ali I.A.M.
- Ali Syamlan
- Aliannejad Rasoul
- Aljawini N.
- AlJohani S.
- Alkwai S.
- Allan A.
- Allan E.
- Allan J.
- Alldis Zoe
- Allen L.
- Allen Meryem
- Allen Schvearn
- Allibone S.
- Allison K.S.
- Allos R.
- Ally S.M.
- AlMalik A.
- Almalki F.
- Almohammed I.
- Almutairi M.
- Alotaibi S.
- Alowayn A.M.
- Alqahtani S.
- Alqubaishi F.
- Alrashed M.
- Alshareef A.
- Alsolm E.
- Alswailm M.
- Altabaibeh A.
- Alvaro A.
- AlZahrani D.
- Amin V.
- Amirsavadkouhi Ali
- Amitrano Sara
- Anastasescu E.
- Anderson F.
- Anderson J.
- Anderson Madeleine
- Anderson Peter
- Anderson S.
- Anderson S.
- Anderson T.
- Andolfo I.
- Andretta F.
- Andreucci E.
- Andrew Angela
- Andrew B.
- Andrew Gratrix
- Andrews E.
- Andrews Shea J.
- Anedda F.
- Anemoli V.
- Annis A.
- Antcliffe David
- Antinori Andrea
- Antoni M.D.
- Anumakonda V.
- Apetri E.
- Aquino Maia
- Arabi Y.M.
- Aravindan Latha
- Arbane Gill
- Archer Katie
- Arden T.
- Arias Sonia Sousa
- Arif S.
- Armstrong Jacob
- Armstrong Lisa
- Armstrong Ruth
- Arning N.
- Arnold Sophie
- Arranz María Jesús
- Arribas E.
- Artuso R.
- Arumugam Prabhu
- Ascolillo Steven
- Ashraf Saima
- Ashton L.
- Aslibekyan S.
- Astin-Chamberlain Raine
- Atkinson E.G.
- Attwood B.
- Aucella F.
- Auld D.
- Auld F.
- Austin Karen
- Austin Pauline
- Auton A.
- Ayers A.
- Azarzar S.
- Bachetti T.
- Baikady R.R.
- Baillie John Kenneth
- Baines Balvinder
- Baines D.
- Baines K.
- Baird Yolanda
- Bakthavatsalam Dhanalakshmi
- Balaconis Mary K.
- Baldassarri M.
- Ball C.A.
- Baltzell A.H.
- Bamford A.
- Bamford Peter
- Banach Dorota
- Bancroft Hollie
- Band G.
- Bandini M.
- Bandla Nageswar
- Bano S.
- Baptista David
- Barakeh D.
- Baras Aris
- Baratti S.
- Barber R.
- Barberis L.
- Barbieri C.
- Barclay Lucy
- Bargagli E.
- Barhoush E.
- Barker J.
- Barnes K.C.
- Baroni S.
- Barrett F.
- Barron A.
- Barry P.
- Bartels M.
- Bartley Shauna
- Baruah R.
- Bashyal Archana
- Basikolo C.
- Bassetti M.
- Bastion V.
- Bates H.
- Bates Michelle
- Batini Chiara
- Battle Ceri
- Bauchmuller K.
- Baxter N.
- Baya N.
- Bayo L.A.
- Beadle Jane
- Bean S.
- Beaumont K.
- Beavis S.
- Beck A.
- Beckmann Noam D.
- Bedini J. L.
- Bee Catherine E.
- Beech E.
- Beech Valerie
- Beekes M.
- Beesley K.
- Begg Colin
- Beguin Y.
- Behan T.
- Beith C.M.
- Belagodu Zakaula
- Belbin Gillian Morven
- Belfield H.
- Belhaj Y.
- Beligni G.
- Belisle A.
- Bell D.
- Bell G.
- Bell M.
- Bell S.
- Bellamy Mary
- Belli M.A.
- Bellini A.
- Bellwood R.
- Below Jennifer
- Bemand T.
- Benetti E.
- Benham Leonie
- Bennett D.
- Bennett Sara
- Bentley David
- Bentley M.
- Benyon S.
- Beranova E.
- Bercades G.
- Bergantini L.
- Bergomi P.
- Berkowitz Nathan
- Bernardo D.
- Bevan E.
- Bewley J.
- Bhatia Nikhil
- Bhatterjee Ravi
- Bhuie Parminder
- Bi R.
- Biagio A.D.
- Bianchi F.
- Bibert S.
- Bibi Fatima
- Biddle Jack
- Biggs Heather
- Birch J.
- Birch J.
- Birch Sophie.
- Birchall K.
- Birchall K.
- Bird S.
- Birkinshaw Isobel
- Birt M.
- Biscarini F.
- Black E.
- Black K.
- Blackledge B.
- Blackman H.
- Blakemore H.
- Blay Natalia
- Blow Sara
- Blunt M.
- Board S.
- Bochud P.Y.
- Bociek Aneta
- Boezen M.
- Boillat N.
- Bokhari M.
- Bolton Matthew
- Bolton Rachel
- Bonner Stephen
- Booker L.
- Borislavova B.
- Borra Catherine
- Botello A.
- Botfield Liam
- Bottà G.
- Bouab M.
- Bough L.
- Boughton A.P.
- Bowes A.
- Bowles Ruth
- Boyle P.
- Boyle R.
- Boz Ceilia
- Bradford Y.
- Bradley C.
- Bradley P.
- Bradley-Potts Joanne
- Bradshaw Zena
- Brady A.
- Brady M.
- Brady R.
- Brandwood C.
- Branney D.
- Brantwood Craig
- Brassard N.
- Brayne A.
- Brealey D.
- Bremmer P.
- Brenner B.
- Bretherick Andrew D.
- Brett Michael
- Brett Stephen
- Brickell K.
- Bridgett V.
- Brimfield Lutece
- Brinkworth Elaine
- Briton Kate
- Britvan Bari
- Bromley M.
- Brooke Hollie
- Brooks S.
- Brown A.
- Brown Adam
- Brown C.W.
- Brown Ellen
- Brown Joanna
- Bruce M.
- Brumpton Ben M.
- Bruno Raffaele
- Brunton Mark
- Bruttini M.
- Bryant J.
- Bryant S.
- Buckley C.
- Buckley Sarah
- Bunni L.
- Burda D.
- Buring Julie E
- Burn I.
- Burnett C.
- Burns K.
- Burt K.
- Burtenshaw Andrew
- Burton Maudrian
- Busani S.
- Bussotti M.
- Butcher D.
- Butler Aaron
- Butler Joanna
- Butler S.
- Butler-Laporte G.
- Butterworth A.S.
- Butterworth-Cowin N.
- Button H.
- Buxbaum Joseph D
- Cabrelli Louise
- Cagova L.
- Caldarelli G.P.
- Callaghan Marie
- Callier S.
- Cameli Paolo
- Campbell Archie
- Campbell Archie
- Campbell Helen
- Campbell Rachael
- Campbell Suzanne
- Campos Sara
- Camsooksai J.
- Canaccini A.
- Cantarini L.
- Cantor M.N.
- Capasso M.
- Capitani K.
- Cappelli S.
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- Carbral-Ortega L.
- Carella M.
- Carey D.J.
- Carmody Margaret
- Carmody S.
- Carnahan M.
- Carreras A.
- Carriero M.L.
- Carter A.
- Carter David
- Carter E.
- Carter Joseph
- Carter S.
- Carungcong J.
- Casey Matt
- Castaño-Vinyals G.
- Castelli F.
- Castle K.
- Castori M.
- Caswell Melanie
- Catena E.
- Caterson Jess
- Cathcart Susanne
- Catlow L.
- Caulfield Mark J.
- Cavazza Anna
- Cawley Kathryn
- Cawthron K.
- Ceri S.
- Chablani M.
- Chadbourn Indra
- Chamnanphon Monpat
- Chan Georgia
- Chan R.
- Chandler B.
- Chang Xiao
- Chapman Susan
- Chariyavilaskul Pajaree
- Charles B.
- Charlesworth Ruth
- Charney Alexander W.
- Charnock R.
- Chasman D.I.
- Chassé M.
- Chaudhary Kumardeep
- Chavan S.
- Cheema Yusuf
- Chen Hung-Hsin
- Chen Jiantao
- Cheng N.
- Cherian Shiney
- Chetam L.
- Chetruengchai Wanna
- Cheyne C.
- Childs D.
- Chittoor G.
- Cho Judy H.
- Cho K.
- Choi Sam
- Choudhury Yasmin
- Christine Almaden-Boyle None
- Chukkambotla Srikanth
- Churchhouse C.
- Chwialkowska Karolina
- Claassen S.
- Clamp Sarah
- Clapham M.
- Claringbould A.
- Clark Amy
- Clark M.
- Clark Martynn
- Clark Richard
- Clark Sarah
- Clark Victoria
- Clarke D.
- Clarke N.
- Clarkson M.
- Clayton Sarah
- Clement Ian
- Clements S.
- Coates Charlotte
- Cockrell Maeve
- Coetzee S.
- Coghlan Phoebe
- Coignet M.
- Coiro G.
- Coker D.
- Cole J.
- Cole J.
- Cole Stephen
- Coleman Dabheoc
- Coles Holly
- Colley Julie
- Collier D.
- Collier David
- Collins Amy
- Collins Brett L.
- Collins C.
- Collins E.
- Collins E.
- Collins Katy
- Collins Rebecca
- Collis M.
- Colobrán R.
- Colombo R.
- Combes Edward
- Connolly K.
- Conticini E.
- Convery K.
- Conyngham J.A.
- Cooper J.
- Cooper L.
- Corcoran Eleanor
- Cordioli Mattia
- Cornell S.
- Corral M.A.
- Corridi M.
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- Åsvold Bjørn Olav
- Publication venue
- Publication date
- 01/01/2022
- Field of study
Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization 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