5 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.
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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
Get PDFCritical 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
Systematic Evaluation of Whole Genome Sequence-Based Predictions of Salmonella Serotype and Antimicrobial Resistance
- Author
- Publication venue
- 'Frontiers Media SA'
- Publication date
- 03/04/2020
- Field of study
No full textWhole-genome sequencing (WGS) is used increasingly in public-health laboratories for typing and characterizing foodborne pathogens. To evaluate the performance of existing bioinformatic tools for in silico prediction of antimicrobial resistance (AMR) and serotypes of Salmonella enterica, WGS-based genotype predictions were compared with the results of traditional phenotyping assays. A total of 111 S. enterica isolates recovered from a Canadian baseline study on broiler chicken conducted in 2012-2013 were selected based on phenotypic resistance to 15 different antibiotics and isolates were subjected to WGS. Both SeqSero2 and SISTR accurately determined S. enterica serotypes, with full matches to laboratory results for 87.4 and 89.2% of isolates, respectively, and partial matches for the remaining isolates. Antimicrobial resistance genes (ARGs) were identified using several bioinformatics tools including the Comprehensive Antibiotic Resistance Database – Resistance Gene Identifier (CARD-RGI), Center for Genomic Epidemiology (CGE) ResFinder web tool, Short Read Sequence Typing for Bacterial Pathoge
Evolution of genes and genomes on the Drosophila phylogeny
- Author
- Abad J.P. (Jose P.)
- Abdouelleil A. (Amr)
- Abdulkadir J. (Jamal)
- Abebe A. (Adal)
- Abera B. (Brikti)
- Abreu J. (Justin)
- Abt D.N. (Dawn N.)
- Adryan B. (Boris)
- Aftuck L. (Lynne)
- Aguade M. (Montserrat)
- Akashi H. (Hiroshi)
- Alexander A. (Allen)
- Alvarez P. (Pablo)
- An P. (Peter)
- Anderson E. (Erica)
- Anderson S. (Scott)
- Anderson W.W. (Wyatt W.)
- Aquadro C.F. (Charles F.)
- Arachi H. (Harindra)
- Ardell D.H. (David H.)
- Arguello R. (Roman)
- Artieri C.G. (Carlo G.)
- Azer M. (Marc)
- Bachantsang P. (Pasang)
- Baldwin J. (Jennifer)
- Barbash D.A. (Daniel A.)
- Barker D. (Daniel)
- Barry A. (Andrew)
- Barsanti P. (Paolo)
- Batterham P. (Phil)
- Batzoglou S. (Serafim)
- Bayul T. (Tashi)
- Begun D. (Dave)
- Bergman C.M. (Casey M.)
- Berlin A. (Aaron)
- Bernardo De Carvalho A. (A.)
- Bessette D. (Daniel)
- Bhutkar A. (Arjun)
- Blanco E. (Enrico)
- Bloom T. (Toby)
- Blye J. (Jason)
- Boguslavskiy L. (Leonid)
- Bonnet C. (Claude)
- Bosak S.A. (Stephanie A.)
- Boukhgalter B. (Boris)
- Bourzgui I. (Imane)
- Bradley R.K. (Robert K.)
- Brand A.D. (Adrianne D.)
- Brent M.R. (Michael R.)
- Brockman W. (Will)
- Brooks A.N. (Angela N.)
- Brown A. (Adam)
- Brown R.H. (Randall H.)
- Butler J. (Jonathan)
- Butlin R.K. (Roger K.)
- Caggese C. (Corrado)
- Cahill P. (Patrick)
- Calvi B.R. (Brian R.)
- Caspi A. (Anat)
- Castrezana S. (Sergio)
- Celniker S.E. (Susan E.)
- Chang J.L. (Jean L.)
- Channer S. (Sheridon)
- Chapple C. (Charles)
- Chatterji S. (Sourav)
- Cheshatsang Y. (Yama)
- Chin C. (Cheewhye)
- Chinwalla A. (Asif)
- Christophe Acer S. (St)
- Chuda L. (Lisa)
- Citroen M. (Mieke)
- Civetta A. (Alberto)
- Clark A.G. (Andrew G.)
- Clifton S.W. (Sandra W.)
- Collymore A. (Alville)
- Comeron J.M. (Josep M.)
- Cooke P. (Patrick)
- Costello J.C. (James C.)
- Costello M. (Maura)
- Coyne J.A. (Jerry A.)
- Craig Venter J. (J.)
- D'Aco K. (Katie)
- Daub J. (Jennifer)
- David R.G. (Robert G.)
- Daza R. (Riza)
- De Haan G. (Georgius)
- Degray S. (Stuart)
- Delcher A.L. (Arthur L.)
- Delehaunty K. (Kim)
- Demaso C. (Christina)
- Dhargay N. (Norbu)
- Do C.B. (Chuong B.)
- Dooley E. (Erin)
- Dooley K. (Kimberly)
- Doricent M. (Missole)
- Dorje P. (Passang)
- Dorjee K. (Kunsang)
- Dupes A. (Alan)
- Ebling H. (Heather)
- Edwards K. (Kevin)
- Eickbush T. (Thomas)
- Eisen M.B. (Michael B.)
- Elong R. (Richard)
- Erii Husby M. (M.)
- Evans J.D. (Jay D.)
- Falk J. (Jill)
- Farina A. (Abderrahim)
- Faro S. (Susan)
- Ferguson D. (Diallo)
- Filipski A. (Alan)
- Findeiß S. (Sven)
- Fisher S. (Sheila)
- Foley C.D. (Chelsea D.)
- Franke A. (Alicia)
- Freyhult E. (Eva)
- Friedrich D. (Dennis)
- Fulton L. (Lucinda)
- Fulton R. (Robert)
- Gadbois L. (Loryn)
- Garcia A.C.L. (Ana C. L.)
- Gardiner A. (Anastasia)
- Garfield D.A. (David A.)
- Garvin B.E. (Barry E.)
- Gearin C.R. (Christina R.)
- Gearin G. (Gary)
- Gelbart W. (William)
- Giannoukos G. (Georgia)
- Gibson G. (Greg)
- Gilbert D. (Don)
- Gnerre S. (Sante)
- Godfrey J. (Jennifer)
- Good R. (Robert)
- Goode T. (Tina)
- Gotea V. (Valer)
- Grabherr M. (Manfred)
- Graham J. (Joseph)
- Grandbois E. (Edward)
- Gravely B. (Brenton)
- Greenberg A.J. (Anthony J.)
- Grewal S. (Sharleen)
- Griffiths-Jones S. (Sam)
- Gross S. (Samuel)
- Guigo R. (Roderic)
- Gustafson E.A. (Erik A.)
- Gyaltsen K. (Kunsang)
- Haerty W. (Wilfried)
- Hafez N. (Nabil)
- Hagos B. (Birhane)
- Hahn M.W. (Matthew W.)
- Hall J. (Jennifer)
- Halligan D.L. (Daniel L.)
- Halpern A.L. (Aaron L.)
- Halter G.M. (Gillian M.)
- Han M.V. (Mira V.)
- Heger A. (Andreas)
- Henson C. (Charlotte)
- Hillier L. (LaDeana)
- Hinrichs A.S. (Angie S.)
- Hollinger A. (Andrew)
- Holmes I. (Ian)
- Honan T. (Tracey)
- Hoskins R.A. (Roger A.)
- Huard M.D. (Monika D.)
- Hubisz M.J. (Melissa J.)
- Hughes L. (Leanne)
- Hultmark D. (Dan)
- Huntley M.A. (Melanie A.)
- Hurhula B. (Brian)
- Iyer V.N. (Venky N.)
- Jaffe D.B. (David B.)
- Jagadeeshan S. (Santosh)
- Jeck W.R. (William R.)
- Johnson J. (Justin)
- Jones C.D. (Corbin D.)
- Jordan W.C. (William C.)
- Ka-Shu Wong G. (Gane)
- Kamat A. (Asha)
- Kanga B. (Ben)
- Karpen G.H. (Gary H.)
- Kashin S. (Seva)
- Kataoka E. (Eiko)
- Kaufman T.C. (Thomas C.)
- Keightley P.D. (Peter D.)
- Kellis M. (Manolis)
- Khazanovich D. (Dmitry)
- Kheradpour P. (Pouya)
- Kirkness E.F. (Ewen F.)
- Kisner P. (Peter)
- Kleber M. (Michael)
- Koerich L.B. (Leonardo B.)
- Kristiansen K. (Karsten)
- Kudrna D. (Dave)
- Kulathinal R.J. (Rob J.)
- Kumar S. (Sudhir)
- Kwok R. (Roberta)
- Lance K. (Krista)
- Lander E. (Eric)
- Langley C.H. (Charles H.)
- Lapoint R. (Richard)
- Lara M. (Marcia)
- Larracuente A.M. (Amanda M.)
- Lazzaro B.P. (Brian P.)
- Lee S.-J. (So-Jeong)
- Lee W. (William)
- Lennon N. (Niall)
- Letendre F. (Frances)
- Levesque L. (Lisa)
- Levine R. (Rosie)
- Li R. (Ruiqiang)
- Lin C.-F. (Chiao-Feng)
- Lin M.F. (Michael F.)
- Lindblad-Toh K. (Kerstin)
- Lipovsky A. (Alex)
- Liu J. (Jinlei)
- Liu S. (Shangtao)
- Liu X. (Xiaohong)
- Llopart A. (Ana)
- Lokyitsang T. (Tashi)
- Lokyitsang Y. (Yeshi)
- Long M. (Manyuan)
- Low L. (Lloyd)
- Lozovsky E. (Elena)
- Lu J. (Jian)
- Lubonja R. (Rakela)
- Lui A. (Annie)
- Luo M. (Meizhong)
- MacCallum I. (Iain)
- MacDonald P. (Pen)
- Machado C.A. (Carlos A.)
- Magnisalis V. (Vasilia)
- Makalowski W. (Wojciech)
- Markiewicz E. (Eva)
- Markow T.A. (Therese A.)
- Maru K. (Kebede)
- Marzo M. (Mar)
- Matsuda M. (Muneo)
- Matthews C. (Charles)
- Matzkin L. (Luciano)
- Mauceli E. (Evan)
- McAllister B. (Bryant)
- McBride C.S. (Carolyn S.)
- McCusker W. (William)
- McDonough S. (Susan)
- McKernan B. (Brendan)
- McKernan K. (Kevin)
- Mehta T. (Teena)
- Meldrim J. (James)
- Mendez-Lago M. (Maria)
- Meneus L. (Louis)
- Mihai O. (Oana)
- Mihalev A. (Atanas)
- Mihova T. (Tanya)
- Minx P. (Patrick)
- Mittelman R. (Rachel)
- Mlenga V. (Valentine)
- Mollenhauer M.U. (Michael U.)
- Montmayeur A. (Anna)
- Montooth K. (Kristi)
- Mount S.M. (Stephen M.)
- Mu X. (Xu)
- Mulrain L. (Leonidas)
- Myers E. (Eugene)
- Navidi A. (Adam)
- Naylor J. (Jerome)
- Negash T. (Tamrat)
- Negre B. (Barbara)
- Newfeld S. (Stuart)
- Nguyen N. (Nga)
- Nguyen T. (Thu)
- Nicol R. (Robert)
- Nielsen R. (Rasmus)
- Noor M.A.F. (Mohamed A. F.)
- Norbu C. (Choe)
- Norbu N. (Nyima)
- Novod N. (Nathaniel)
- O'Grady P. (Patrick)
- O'Neill B. (Barry)
- Oliver B. (Brian)
- Osman S. (Sahal)
- Oyono O.L. (Otero L.)
- Pachter L. (Lior)
- Papaceit M. (Montserrat)
- Parisi M. (Michael)
- Parisi M.J. (Matthew J.)
- Parts L. (Leopold)
- Patti C. (Christopher)
- Pedersen J.S. (Jakob S.)
- Pesole G. (Graziano)
- Phillippy A.M. (Adam M.)
- Phunkhang P. (Pema)
- Pierre F. (Fritz)
- Pollard D.A. (Daniel A.)
- Ponting C.P. (Chris P.)
- Pop M. (Mihai)
- Porcelli D. (Damiano)
- Powell J.R. (Jeffrey R.)
- Priest M. (Margaret)
- Prohaska S. (Sonja)
- Pruitt K. (Kim)
- Puig M. (Marta)
- Quesneville H. (Hadi)
- Raghuraman S. (Sujaa)
- Rand D. (David)
- Rasmussen M.D. (Matthew D.)
- Ravi Ram K. (Kristipati)
- Reed L.K. (Laura K.)
- Reenan R. (Robert)
- Rege F. (Filip)
- Reily A. (Amy)
- Remington K.A. (Karin A.)
- Reyes R. (Rebecca)
- Rieger T.T. (Tania T.)
- Rise C. (Cecil)
- Ritchie M.G. (Michael G.)
- Robin C. (Charles)
- Rogers Y.-H. (Yu-Hui)
- Rogov P. (Peter)
- Rohde C. (Claudia)
- Ross K. (Keenan)
- Rozas J. (Julio)
- Rubenfield M.J. (Marc J.)
- Ruiz A. (Alfredo)
- Russo S. (Susan)
- Ryan E. (Elizabeth)
- Sackton T.B. (Timothy B.)
- Salzberg S.L. (Steven L.)
- Sanchez-Gracia A. (Alejandro)
- Saranga D.J. (David J.)
- Sato H. (Hajime)
- Schaeffer S.W. (Stephen W.)
- Schatz M.C. (Michael C.)
- Schlenke T. (Todd)
- Schwartz R. (Russell)
- Segarra C. (Carmen)
- Settipalli S. (Sampath)
- Shea T. (Terry)
- Sherpa N. (Ngawang)
- Shi L. (Lu)
- Shih D. (Diana)
- Singh N.D. (Nadia D.)
- Singh R.S. (Rama S.)
- Sirot L. (Laura)
- Sirota M. (Marina)
- Sisneros N.B. (Nicholas B.)
- Smith C.D. (Chris D.)
- Smith D.R. (Douglas R.)
- Smith T.F. (Temple F.)
- Sparrow T. (Todd)
- Spaulding J. (Jessica)
- Spieth J. (John)
- Stage D.E. (Deborah E.)
- Stalker J. (John)
- Stange-Thomann N. (Nicole)
- Stark A. (Alexander)
- Stavropoulos S. (Sharon)
- Stephan W. (Wolfgang)
- Stone C. (Catherine)
- Strader C. (Christopher)
- Strausberg R.L. (Robert L.)
- Strempel S. (Sebastian)
- Sturgill D. (David)
- Sutton G. (Granger)
- Sutton G.G. (Granger G.)
- Tao W. (Wei)
- Teichmann S. (Sarah)
- Tesfaye S. (Senait)
- Thomson T. (Talene)
- Thoulutsang D. (Dawa)
- Thoulutsang Y. (Yama)
- Tobari Y.N. (Yoshiko N.)
- Tomimura Y. (Yoshihiko)
- Topham K. (Kerri)
- Topping I. (Ira)
- Tsamla T. (Tsamla)
- Tsolas J.M. (Jason M.)
- Valente V.L.S. (Vera L. S.)
- Vassiliev H. (Helen)
- Venter E. (Eli)
- Vicario S. (Saverio)
- Vieira F.G. (Filipe G.)
- Vilella A.J. (Albert J.)
- Villasante A. (Alfredo)
- Vo A. (Andy)
- Walenz B. (Brian)
- Wang J. (Jun)
- Wangchuk T. (Tsering)
- Wangdi T. (Tsering)
- Wasserman M. (Marvin)
- Watts T. (Thomas)
- Weiand M. (Michael)
- Wilkinson J. (Jane)
- Wilson A. (Adam)
- Wilson D. (Derek)
- Wilson R.K. (Richard K.)
- Wing R.A. (Rod A.)
- Wolfner M.F. (Mariana F.)
- Wong A. (Alex)
- Wu C.-I. (Chung-I)
- Wu G. (Gabriel)
- Yadav S. (Shailendra)
- Yamamoto D. (Daisuke)
- Yang H.-P. (Hsiao-Pei)
- Yang S.-P. (Shiaw-Pyng)
- Yorke J.A. (James A.)
- Yoshida K. (Kiyohito)
- Young G. (Geneva)
- Yu Q. (Qing)
- Zdobnov E. (Evgeny)
- Zembek L. (Lisa)
- Zhang P. (Peili)
- Zhang Y. (Yu)
- Zhong D. (Danni)
- Zimin A.V. (Aleksey V.)
- Zimmer A. (Andrew)
- Zwirko Z. (Zac)
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 08/11/2007
- Field of study
No full textComparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species
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.
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- Zamikula J.
- Zanella I.
- Zborowski A.C.
- Zeberg Hugo
- Zechner Marie
- Zguro K.
- Zhang M.
- Zhao J.H.
- Zheng Chenqing
- Zhou W.
- Zitter L.
- Zlatopolsky Menachem
- Zongo Olivier
- Zucchi P.
- Zyndorf Marissa
- Zöllner S.
- Åsvold Bjørn Olav
- Publication venue
- Publication date
- 01/01/2022
- Field of study
No full textAltres 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
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- Publication venue
- 'Informa UK Limited'
- Publication date
- Field of study
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