GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19 (2023)

Type of publication:
Journal article

Author(s):
Pairo-Castineira E.; Rawlik K.; Bretherick A.D.; Qi T.; Wu Y.; Nassiri I.; McConkey G.A.; Klaric L.; Kousathanas A.; Richmond A.; Malinauskas T.; Thwaites R.; Morrice K.; Maslove D.; Semple M.G.; Knight J.; Hinds C.; Horby P.; Ling L.; McAuley D.; Montgomery H.; Openshaw P.J.M.; Begg C.; Walsh T.; Tenesa A.; Flores C.; Riancho J.A.; Rojas-Martinez A.; Clohisey S.; Millar J.; Aitkin E.; Aravindan L.; Armstrong R.; Biggs H.; Boz C.; Chikowore P.; Coutts A.; Coyle J.; Cullum L.; Das S.; Day N.; Donnelly L.; Duncan E.; Finernan P.; Fourman M.H.; Furlong A.; Furniss J.; Gallagher B.; Gilchrist T.; Golightly A.; Griffiths F.; Hafezi K.; Hamilton D.; Hendry R.; Kearns N.; Law D.; Law R.; Law S.; Lidstone-Scott R.; Lauder C.; Macgillivray L.; Maclean A.; Mal H.; McCafferty S.; McMaster E.; Meikle J.; Murphy S.; Mybaya H.; Oosthuyzen W.; Zheng C.; Chen J.; Parkinson N.; Paterson T.; Tucker P.; Schon K.; Stenhouse A.; Das M.; Swets M.; Szoor-McElhinney H.; Taneski F.; Turtle L.; Wackett T.; Ward M.; Weaver J.; Wrobel N.; Zechner M.; Pan J.; Grau N.; Jones T.O.; Lim R.; Marotti M.; Whitton C.; Bociek A.; Campos S.; Arbane G.; Shankar-Hari M.; Ostermann M.; Cha M.; DAmato F.; Kosifidou E.; Lorah S.; Morera K.; Brady L.; Hugill K.; Henning J.; Bonner S.; Headlam E.; List A.; Morley J.; Welford A.; Kamangu B.; Ratnakumar A.; Shoremekun A.; Alldis Z.; Astin-Chamberlain R.; Bibi F.; Biddle J.; Blow S.; Bolton M.; Borra C.; Bowles R.; Burton M.; Choudhury Y.; Cox A.; Ebano P.; Fotiadis S.; Gurasashvili J.; Halls R.; Hartridge P.; Kallon D.; Kassam J.; Lancoma-Malcolm I.; Matharu M.; May P.; Mitchelmore O.; Newman T.; Patel M.; Pheby J.; Pinzuti I.; Prime Z.; Prysyazhna O.; Shiel J.; Tierney C.; Zongo O.; Zak A.; Mundy M.; Thompson C.; Pritchard L.; Gellamucho M.; Cartlidge D.; Bandla N.; Bailey L.; Delaney J.; Scott L.; Abdelrazik M.; Alasdair F.; Carter D.; Elhassan M.; Ganesan A.; Lamond Z.; Purohit D.; Rohit K.; Saleem M.; Wall A.; Xavier K.; Bakthavatsalam D.; Gehad K.; Gnanapragasam P.; Jain K.; Jain S.; Malik A.; Pappachan N.; Moreno-Cuesta J.; Haldeos A.; Vincent R.; Oziegb M.; Cavazza A.; Cockrell M.; Corcoran E.; Depante M.; Finney C.; Jerome E.; Knighton A.; Nayak M.; Pappa E.; Saha S.; Dodd A.; O'Reilly K.; McPhail M.; Clarey E.; Noble H.; Coghlan P.; Brett S.; Gordon A.; Templeton M.; Antcliffe D.; Banach D.; Darnell S.; Fernandez Z.; Jepson E.; Mohammed A.; Rojo R.; Arias S.S.; Gurung A.T.; Fernandez-Roman J.; Hamilton D.O.; Johnson E.; Johnston B.; Martinez M.L.; Mulla S.; Waite A.A.C.; Williams K.; Waugh V.; Welters I.; Emblem J.; Norris M.; Shaw D.; Bashyal A.; Beer S.; Hutton P.; McKechnie S.; Davidson N.; Readion G.; Ryu J.; Wilson J.; Agrawal S.; Elston K.; Jones M.; Meaney E.; Polgarova P.; Elbehery M.; Summers C.; Daubney E.; Ng A.; Marshall J.; Pathan N.; Stroud K.; White D.; Andrew A.; Ashraf S.; Dent M.; Langley M.; Peters C.; Ryan L.; Sampson J.; Wei S.; Baddeley A.; Meredith M.; Morris L.; Gibbons A.; McLoughlin L.; Delgado C.C.; Clark V.; Dawson D.; Ding L.; Durrant G.; Ezeobu O.; Hurt W.J.; Kanu R.; Kinch A.; Leaver S.; Lisboa A.; Mathew J.; Patel K.; Saluzzio R.P.; Rawlins J.; Samakomva T.; Shah N.; Sicat C.; Texeira J.; De Queiroz J.G.; Da Gloria E.F.; Maccacari E.; Yun N.; Manna S.; Farnell-Ward S.; Maizcordoba M.; Thanasi M.; Ali H.H.; Hastings J.; Grauslyte L.; Hussain M.; Ruge B.; King S.; Pogreban T.; Rosaroso L.; Smith H.; Phull M.-K.; *Adams N.; Franke G.; George A.; Salciute E.; Wong J.; Dunne K.; Flower L.; Sharland E.; Sra S.; Andrew G.; Callaghan M.; Barclay L.; Baillie K.; Hope D.; Mcculloch C.; Allen M.; Baptista D.; Crowe R.; Fox J.; Khera J.; Loveridge A.; McKenley I.; Morino E.; Naranjo A.; O'Connor D.; Simms R.; Sollesta K.; Swain A.; Herdman-Grant R.; Joseph A.; Nown A.; Rose S.; Pogson D.; Boxall H.; Brimfield L.; Claridge H.; Daly Z.; George S.; Gribbin A.; Cheema Y.; Cutler S.; Richards O.; Roynon-Reed A.; Cherian S.; Heron A.E.; Williams G.; Szakmany T.; Waters A.; Dunhill J.; Jones F.; Morris R.; Ship L.; Cardwell A.; Ali S.; Bhatterjee R.; Bolton R.; Chukkambotla S.; Coleman D.; Dalziel J.; Dykes J.; Fine C.; Gay B.; Goddard W.; Goodchild D.; Harling R.; Hijazi M.; Keith S.; Khan M.; Matt R.; Ryan-Smith J.; Saad S.; Springle P.; Thomas J.; Truman N.; Kazi A.; Smith M.; Collier H.; Davison C.; Duberley S.; Hargreaves J.; Hartley J.; Patel T.; Kent A.; Goodwin E.; Zaki A.; Tibke C.; Hopkins S.; Gerrard H.; Jackson M.; Bennett S.; Mills R.; Bell J.; Campbell H.; Dawson A.; Dodds S.; Duffy S.; Gallagher L.; McCafferty G.; Short S.; Thomas K.; Walker C.; Reynolds J.; Yates B.; McKie H.; Panteli M.; Thompson M.; Waddell G.; De Beger S.; Abraheem A.; Dunmore C.; Girach R.; Jones R.; London E.; Nagra I.; Nasir F.; Sainsbury H.; Smedley C.; Brearey S.; Burchett C.; Faulkner M.; Jeffrey H.; Bamford P.; Shaikh F.; Slack L.; Davies A.; Brooke H.; Suarez J.C.; Charlesworth R.; Hansson K.; Norris J.; Poole A.; Sandhu R.; Smithson E.; Thirumaran M.; Wagstaff V.; Buckley S.; Sloan B.; Rose A.; Major A.; Metcalfe A.; Almaden-Boyle C.; Austin P.; Chapman S.; Eros A.; Cabrelli L.; Cole S.; Whyte C.; Casey M.; Bafitis V.; Tsinaslanidis G.; George C.; Khade R.; Black C.; Ashok S.R.; Farley S.; Brinkworth E.; Harford R.; Murphy C.; Williams M.; Newey L.; Toghill H.; Lewis S.; Rees T.; Battle C.; Baker M.; Travers J.; Chesters K.; Baxter N.; Arnott A.; McCreath G.; Rooney L.; Sim M.; Henderson S.; Dalton C.; Kennedy-Hay S.; O'Donohoe L.; O'Hare M.; Orlikowska I.; McNeela F.; Lyle A.; Hughes A.; Radhakrishnan J.; Gibson S.; Bancroft H.; Bellamy M.; Daglish J.; Kadiri S.; Moore F.; Rhodes J.; Sangombe M.; Peterkin Z.; Carmody M.; Cottle J.; Peasgood E.; de Gordoa L.O.-R.; Cinquina Z.; Howard K.; Joy R.; Roche S.; Birkinshaw I.; Carter J.; Ingham J.; Marshall N.; Pearson H.; Scott Z.; Dasgin J.; Gill J.; Nilsson A.; Hull D.; Ahmadhaider N.; Bates M.; McGhee C.; Ellis H.; Howe G.S.; Singh J.; Stroud N.; Lynch C.; Krishnamurthy V.; Lim L.; Jha R.; Egan J.; Felton T.; Glasgow S.; Padden G.; Choudhr O.; Moss S.; Lingeswaran S.; Alexander P.; Fiouni S.; Ward L.; Allen S.; Shaw J.; Smith C.; Adanini O.; Collins R.; Msiska M.; Ofori L.; Bhatia N.; Dolan H.; Brunton M.; Caterson J.; Coles H.; Keating L.; Tilney E.; Jacques N.; Frise M.; Armistead J.; Bartley S.; Bhuie P.; Rai S.; Tomkova G.; Greer S.; Shuker K.; Tridente A.; Dobson E.; Tully R.; Dearden J.; Drummond A.; Kamath P.; Mulcahy M.; Munt S.; O'Connor G.; Philbin J.; Rishton C.; Scott C.; Winnard S.; Hasni N.; Gascoyne R.; Hawes J.; Pritchard K.; Stevenson L.; Whileman A.; Beavis S.; Bishop L.; Cart C.; Dale K.; Kelly-Baxter M.; Mendelski A.; Moakes E.; Smith R.; Woodward J.; Wright S.; Allan A.; Botello A.; Liew J.; Medhora J.; Trumper E.; Savage F.; Scott T.; Place M.; Kaye C.; Benyon S.; Marriott S.; Park L.; Quinn H.; Skyes D.; Zitter L.; Baines K.; Gordon E.; Keenan S.; Pitt A.; Duffy K.; Ireland J.; Semple G.; Turner L.; Cathcart S.; Rimmer D.; Puxty A.; Puxty K.; Hurst A.; Miller J.; Speirs S.; Bradshaw Z.; Brown J.; Melling S.; Preston S.; Slawson N.; Warden S.; Beasley A.; Stoddard E.; Benham L.; Cupitt J.; Caswell M.; Elawamy L.; Wignall A.; Roberts B.; Golding H.; Leggett S.; Male M.; Marani M.; Prager K.; Williams T.; Golder K.; Jones O.; Cusack R.; Bolger C.; Burnish R.; Carter M.; Jackson S.; Salmon K.; Biss J.; Aquino M.; Croft M.; Frost V.; White I.; Govender K.; Webb N.; Stapleton L.; Wells C.; Nikitas N.; Sanchez-Rodriguez A.; Spencer K.; Stowe B.; Izzard Y.; Poole M.; Monnery S.; Trotman S.; Beech V.; Combes E.; Joefield T.; Covernton P.; Savage S.; Woodward E.; Camsooksai J.; Reschreiter H.; Barclay C.; DeAth Y.; Dube J.; Humphrey C.; Jenkins S.; Langridge E.; Milne R.; Wadams B.; Woolcock M.; Brett M.; Digby B.; Gemmell L.; Hornsby J.; MacGoey P.; O'Neil P.; Price R.; Sundaram R.; Abel L.; Rodden N.; Thomson N.; Rooney K.; Currie S.; Parker N.; Walker L.; Henderson P.; Ogg B.; Whiteley S.; Wilby L.; Long K.; Matthew S.; Salada S.; Trott S.; Watts S.; Friar Z.; Speight A.; Bastion V.; Chandna H.; Djeugam B.; Haseeb M.; Kent H.; Lubimbi G.; Murdoch S.; David B.; Lorusso R.; Vochin A.; Penacerrada M.; Wulandari R.; Heath C.; Jakkula S.; Morris A.; Ahmed A.; Nune A.; Buttriss C.; Whitaker E.; Davey M.; Golden D.; Acklery A.; Fernandes F.; Seaman B.; Earl V.; Collins A.; Adam R.; Treus E.; Holland S.; Alfonso J.; Bruce M.; Durrans L.J.; Eltayeb A.; Hey S.; Hruska M.; Lamb T.; Rothwell J.; Fitzgerald A.; Lindergard G.; T-Michael H.; Duncan T.; Baxter-Dore S.; Fox C.; Guerin J.; Hodgkiss T.; Connolly K.; McAlinden P.; Bridgett V.; Fearby M.; Gulati A.; Hanson H.; Kelly S.; McCormack L.; Nixon R.; Robinson P.; Slater V.; Stephenson E.; Webster A.; Webster K.; Hays C.; Hudson A.; Clement I.; Davis J.; Francis S.; Jerry D.; Abernathy C.; Foster L.; Gratrix A.; Cabral-Ortega L.; Hines M.; Martinson V.; Stones E.; Winter K.; Barrow E.; Wylie K.; Baines D.; Kolakaluri L.; Clark R.; Sukumaran A.; Brandwood C.; Barker M.; Paripoorani D.; Taylor C.; Downes C.; Hayman M.; Riches K.; Daniel P.; Subramanian D.; Holding K.; Hilton M.; McDonald C.; Richardson G.; Halladay G.; Harding P.; Reddy A.; Turner-Bone I.; Wilding L.; Parker R.; Lloyd M.; Smith L.; Kelly C.; Lazo M.; Neal A.; Walton O.; Melville J.; Naisbitt J.; Bullock E.; Joseph R.; Callam S.; Hudig L.; Keshet-Price J.; Stammers K.; Convery K.; Randell G.; Fottrell-Gould D.; Mwaura E.; Sutherland S.-B.; Stewart R.; Mew L.; Wren L.; Thrasyvoulou L.; Willis H.; Scriven J.; Hopkins B.; Lenton D.; Roberts A.; Bokhari M.; Lucas R.; McCormick W.; Ritzema J.; Linnett V.; Sanderson A.; Wild H.; Flanagan R.; Hull R.; Rhead K.; McKenna E.; Hughes G.; Anderson J.; Jones K.; Latham S.; Riley H.; Coulding M.; Mercer O.; Potla D.; Rehman H.; Savill H.; Turner V.; Jude E.; Kilroy S.; Apetri E.; Basikolo C.; Blackledge B.; Catlow L.; Collis M.; Doonan R.; Harris J.; Harvey A.; Knowles K.; Lee S.; Lomas D.; Lyons C.; McMorrow L.; Michael A.; Pendlebury J.; Perez J.; Poulaka M.; Proudfoot N.; Slevin K.; Thomas V.; Walker D.; Dark P.; Charles B.; McLaughlan D.; Slaughter M.; Horner D.; Cawley K.; Marsden T.; Andrews J.; Beech E.; Akinkugbe O.; Bamford A.; Belfield H.; Jones G.A.L.; McHugh T.; Meghari H.; Ray S.; Tomas A.L.; O'Neill L.; Peters M.; Bell M.; Benkenstein S.; Chisholm C.; Kupiec K.; Payne C.; Halls J.; Blakemore H.; Goff E.; Hayes K.; Smith K.; Stephens D.; Worner R.; Borislavova B.; Faulkner B.; Thomas M.; Cookson R.; Gendall E.; Larman G.; Pope R.; Smalira A.; Priestley V.; Cosier T.; Millen G.; Rand J.; Schumacher N.; Sandhar R.; Weston H.; Richardson N.; Cooper L.; Jones C.; Huang Y.-W.J.; Jacob R.; Denmade C.; McIntyre L.; Trodd D.; Martin J.; Watson G.; Bevan E.; Wreybrown C.; Bano S.; Bellwood R.; Bentley M.; Bromley M.; Gurr L.; Ledgard C.; McGowan J.; Pye K.; Sellick K.; Stacey A.; Warren D.; Wilkinson B.; Akeroyd L.; Shafique H.; Morgan J.; Shorter S.; Swinger R.; Waters E.; Lawton T.; Allan E.; Darlington K.; Davies F.; Davies L.; Easton J.; Kumar S.; Lean R.; Mackay C.; Pugh R.; Qiu X.; Rees S.; Scanlon J.; Lewis J.; Menzies D.; Bolger A.; Davies G.; Davies J.; Garrod E.; Jones H.; Manley R.; Williams H.; Frankham J.; Pitts S.; Branney D.; Tiller H.; Efford G.; Garland Z.; Grimmer L.; Gumbrill B.; Johnson R.; Sweet K.; Bewley J.; Coleman C.; Corcoran K.; Morano E.M.H.; Shiel R.; Webster D.; Bonnici J.; Daniel E.; Dell A.; Kent M.; Wilkinson A.; Brown E.; Kay A.; Campbell S.; Cowton A.; Greenaway V.; Potts K.; Hutton C.; Shepperson A.; Forsey M.; Vertue M.; Riches J.; Kaliappan A.; MacCallum N.; Bercades G.; Hass I.; Martir G.; Reyes A.; Smyth D.; Zapatamartinez M.; Alvaro A.; Jetha C.; Ma L.; Booker L.; Mostoles L.; Pratley A.; Altabaibeh A.; Parmar C.; Gilbert K.; Ferguson S.; Shepherd A.; Morris S.; Singleton J.; Baruah R.; Amamio M.; Birch S.; Briton K.; Clark S.; Doverman K.; Marshall L.; Simpson S.; Lloyd G.; Bell S.; Rivers V.; Purewal B.; Hammerton K.; Oleary R.; Cornell S.; Jarmain J.; Rogerson K.; Wakinshaw F.; Woods L.; Rostron A.; Elcioglu Z.; Roy A.; Bell G.; Dickson H.; Wilcox L.; Katary A.; English K.; Hutter J.; Pawley C.; Doble P.; Shovelton C.; Vaida M.; Purnell R.; Cagova L.; Fofano A.; Holcombe H.; Mitchell A.M.; Mwaura L.; Raman K.P.; Garnr L.; Mepham S.; Paques K.; Vuylsteke A.; Mackie J.; Pearn C.; Zamikula J.; Birt M.; Gude E.T.; Nyirenda M.; Capozzi L.; Reece-Anthony R.; Khaliq W.; Noor H.; Nilo A.C.; Grove M.; Daniel A.; Finn J.; White N.; Saha R.; Badal B.; Ixer K.; Duffin D.; Player B.; Hill H.; Davies M.; Davies R.; Hunt L.; Thomas E.; Oblak M.; Thankachen M.; Irisari J.; Sayan A.; Popescu M.; Finch C.; Jamieson A.; Quinn A.; Cooper J.; Liderth S.; Waddington N.; Burn I.; Manso K.; Penn R.; Tebbutt J.; Thornton D.; Winchester J.; Hambrook G.; Shanmugasundaram P.; Craig J.; Simpson K.; Sibbett L.; Paine S.; Conyngham J.-A.; Mupudzi M.D.; Thomas R.; Wright M.; Griffin D.; Partridge R.; Corral M.A.; Muchenje N.; Sitonik M.; Brown C.W.; Butler A.; Folkes L.; Fox H.; Gardner A.; Helm D.; Hobden G.; King K.; Margalef J.; Margarson M.; Martindale T.; Meadows E.; Raynard D.; Thirlwall Y.; Baird Y.; Gomez R.; Hodgson L.; Corin C.; Sidall E.; Szabo D.; Floyd S.; Davies H.; Austin K.; Kelsall O.; Wood H.; Anderson P.; Archer K.; Burtenshaw A.; Clayton S.; Cother N.; Cowley N.; Davis C.; Digby S.; Durie A.; Harrison A.; Low E.; McAlindon M.; McCurdy A.; Morgan A.; Rankin T.; Thrush J.; Tranter H.; Vigurs C.; Wild L.; Cornell T.; Ralph K.; Bean S.; Burt K.; Spivey M.; Richards C.; Tedstone R.; Carmody S.; Zhao X.; Page V.; Guanco M.L.; Hoxha E.; Zorloni C.; Dean C.; Jones E.; Carter E.; Dunn J.; Kong T.; Mahenthran M.; Marsh C.; Holland M.; Keenan N.; Mahmoud M.; Lyons M.; Bradley-Potts J.; Wassall H.; Young M.; Bradley P.; Burda D.; Donlon S.; Harden L.; Harris C.; Mayangao I.; Montaser R.; Mtuwa S.; Piercy C.; Smith E.; Stone S.; Verula J.; Blackman H.; Marriott C.; Michalak N.; Creagh-Brown B.; Salberg A.; Boyer N.; Pristopan V.; Walker R.; Hormis A.; Collier D.; Graham C.; Maynard V.; McCormick J.; Warrington J.; Cosgrove D.; McFarland D.; Ratcliffe J.; Charnock R.; Wynter I.; Gill M.; Kirk J.; Paul P.; Ratnam V.; Shelton S.; Jardine C.; Hay A.; Williams D.; Deacon B.; Durga L.; Hibbert M.; Kennard-Holden G.; Woodford C.; Pothecary C.; Tetla D.; Agravante K.; Smeaton J.; Price A.; Thomas A.; Thorpe C.; Knights E.; Ward D.; Laha S.; Verlander M.; Williams A.; Prout R.; Langton H.; Watters M.; Hunt C.; Novis C.; Arif S.; Cunningham A.; Hewitt C.; Hindale J.; Jackson-Lawrence K.; Shepardson S.; Wills M.; Butler S.; Tavares S.; Barber R.; Hilldrith A.; Hubbard K.; Egginton D.; Clark M.; Purvis S.; Sinclair S.; Collins V.; Landeg B.; Sell C.; Coetzee S.; Gales A.; Icke B.; Raj M.; Williams C.; Williams J.; Hill L.; Kayani A.; Masunda B.; Gondo P.; Atayeva N.; Cruz C.; Pattison N.; Burnett C.; Hatton J.; Heeney E.; Newton M.; Al-Moasseb H.; Behan T.; Stead R.; Mitra A.; Humphreys S.; Cockerill H.; Tampsett R.; Postovalova E.; Coventry T.; Fowler S.; Macmahon M.; Cochrane P.; Pirie S.; Hanley S.; Ali A.; Brady M.; Dale S.; Dance A.; Gledhill L.; Greig J.; Hanson K.; Holdroyd K.; Home M.; Ishaq T.; Kelly D.; Matapure L.; Melia D.; Mellor S.; Merwaha E.; Nortcliffe T.; Shaw L.; Shaw R.; Wood T.; Bayo L.-A.; Usher M.; Wilson A.; Kitson R.; Pinnell J.; Robinson M.; Boltwood K.; Birch J.; Bough L.; Tutton R.; Winter-Goodwin B.; Goodsell J.; Taylor K.; Williams P.; Williams S.; Cave A.; Rees J.; Imeson-Wood J.; Amin V.; Karthik K.; Kausar R.; Anastasescu E.; Reid K.; Anumakonda V.; Stoddart E.; Demetriou C.; Eckbad C.; Howie L.; Mitchard S.; Ramos L.; White K.; Hierons S.; Kelly F.; Serrano-Ruiz A.; Evans G.; Nicol L.; Wilkins J.; Hulacka K.; Debreceni G.; Crickmore V.; Hill K.; Kannan T.; Dagutao Z.; Beesley K.; Lewis A.; Perry J.; Antony S.; Board S.; Buckley C.; Pippard L.; Tanate A.; Wood D.; Kubisz-Pudelko A.; Gouda A.; Auld F.; Donnachie J.; Murdoch E.; Prentice L.; Runciman N.; Senaratne D.; Short A.; Sweeney L.; Symon L.; Todd A.; Turner P.; McCann E.; Salutous D.; Edmond I.; Whitelaw L.; Venkatesh H.; Bland Y.; Kajtor I.; Kavanagh L.; Singler K.; Linfield-Brown G.; Moore L.S.P.; Vizcaychipi M.; Martins L.; Moore L.; Bull R.; Carungcong J.; Allen L.; Beranova E.; Knight A.; Price C.; Tilbey S.; Turney S.; Hazelton T.; Tutt G.; Arora M.; Turki S.; Sinfield E.; Deery J.; Ramos H.; Cristiano D.; Dormand N.; Farzad Z.; Gummadi M.; Salmi S.; Sloane G.; Varghese M.; Patel B.; Kamal L.; Zborowski A.C.; Coe R.; Anderson M.; Beadle J.; Coates C.; Collins K.; Crowley M.; Johnson L.; King L.; Paramsothy R.; Sargeant J.; Silva P.; Stuart C.; Taylor J.; Tyl D.; Wakefield P.; Kamundi C.; Olufuwa O.; Belagodu Z.; Gherman A.; Oakley N.; Allan J.; Geary T.; Meikle A.; O'Brien P.; Wood S.; Clark A.; Houston G.; Black K.; Clarkson M.; D'Sylva S.; Morrison A.; Norman K.; Taylor M.; Clements S.; Cohrane C.; Gonzalez N.; Strachan D.; Moar K.; Smythe M.; Nichol A.; Brickell K.; Ali I.A.M.; Beaumont K.; Elsaadany M.; Fernandes K.; Ally S.M.; Rangarajan H.; Sarathy V.; Selvanayagam S.; Vedage D.; White M.; Coton Z.; Joshy A.; Blunt M.; Curgenven H.; Botfield L.; Dexter C.; Kuravi A.; Butler J.; Chadwick R.; Ranga P.; Richardson L.; Virgilio E.; Anwer M.; Garg A.; Botfield D.; Marriott X.; Stewart K.; Phillips C.; Nowak J.; Skinner D.; Jones S.; Crawley R.; Crew A.; Cunningham M.; Daniels A.; Harrison L.; Hope S.; Lancaster N.; Matthews J.; Wray G.; Nicholson A.; Inweregbu K.; Cutts S.; Miller K.; Brady A.; Chan R.; McIvor S.; Prady H.; Mathew B.; Little J.; Furniss T.; Wright C.; King B.; Wasson C.; O'Neill A.; Turley C.; McGuigan P.; Collins E.; Finn S.; Green J.; McAuley J.; Nair A.; Quinn C.; Tauro S.; Ward K.; McGinlay M.; Reddy K.; Ahmad N.; Anderson S.; Barker J.; Bauchmuller K.; Birchall K.; Bird S.; Cawthron K.; Chetam L.; Cole J.; Donne B.; Foote D.; Ford A.; Hanratty H.; Harrington K.; Hesseldon L.; Housley K.; Jackson Y.; Jarman C.; Kibutu F.; Lenagh B.; Macharia I.; Masuko S.; Milner L.; Newell H.; Nwafor L.; Oxspring S.; Phillips P.; Raithatha A.; Rowland-Jones S.; Smith J.; Thompson R.; Trower H.; Walker S.; Watson J.; Wiles M.; Lye A.; Willson J.; Mills G.; Harris S.; Hartill E.; Barron A.; Collins C.; Kaul S.; Nolan C.; Polgar O.; Prendergast C.; Rogers P.; Shokkar R.; Woodruff M.; Mahay K.; Thwaites V.; Reed A.; Meyrick H.; Passmore H.; Farwell J.; Brown A.; Gregory J.; Armstrong D.; Bowey A.; Cowley A.; Corner A.; Highgate J.; Rutherfurd C.; Taylor J.-A.; Goodwin S.; Rutherford C.; Eapen B.; Trim F.; Donnison P.; Armstrong L.; Bates H.; Dooks E.; Farquhar F.; Kitching A.; McParland C.; Packham S.; Hairsine B.; Andreou P.; Hales D.; Mathews M.; Patel R.; Barry P.; Flint N.; Hailstone J.; Ghuman N.; Leonard B.; Lees R.; Butcher D.; Leng K.; Butterworth-Cowin N.; O'Sullivan S.; Ghosh A.; Adams C.; *Agasou A.; *Arden T.; *Beekes M.; *Bowes A.; *Boyle P.; *Button H.; *Carnahan M.; *Carter A.; *Childs D.; *Gaylard J.; *Hurford F.; *Hussain Y.; *Javaid A.; *Jones J.; *Leigh M.; *Martin T.; *Millward H.; *Motherwell N.; *Mullan D.; *Newman J.; *Rikunenko R.; *Stickley J.; *Summers J.; *Ting L.; *Tivenan H.; *Donaldson D.; *Capps N.; *Cale E.; *Osbourne W.; *Pajak S.; *Rankin J.; *Tonks L.; Baird T.; Harkins M.; Ruddy J.; West J.; Duffield J.; Mallon L.; Smith O.; Smuts S.; Campbell A.; Davies C.; Davies S.; Jobes L.; Whitehead V.; Watkins C.; Bowman F.; Milligan B.; McPherson L.; Metherell S.; Harris N.; Lake V.; Radford E.; Smallwood A.; Gopal S.; Vassell K.; Bell D.; Boyle R.; Douglas K.; Glass L.; Lennon L.; Rattray A.; Beith C.; Lee E.; Parsons P.; Attwood B.; Jefferson P.; Ranganathan M.; Atwal I.; Campbell B.; Day A.; Stagg C.; Haynes E.; Ahmed C.; Clamp S.; Colley J.; Haq R.; Hayes A.; Joseph S.; Maqsood Z.; Hussain S.; Hulme J.; Domingos P.; Kumar R.; Purewal M.; Taylor B.; Bunni L.; Latif M.; Jennings C.; Jose S.; Marshall R.; Metryka A.; Subramanian G.; Burgoyne A.; O'Connell S.; Tyler A.; Waldron J.; Hilltout P.; Evitts J.; Ward G.; Bremmer P.; Hawkins C.; Jackman S.; Ogorek M.; Ashby K.; Thornton L.; Mercer P.; Halkes M.; Revill A.; Saint B.; Fletcher J.; Netherton K.; Chablani M.; Kirkby A.; Roper A.; Szymiczek K.; Sutherland I.; O'Brien L.; Connell J.; Davies K.; Lewis T.; Omar Z.; Perkins E.; Roche L.; Sathe S.; Davies E.; Lyon A.; Mapfunde I.; Willis C.; Hitchcock R.; Hall K.; King C.; Fagan A.; Nazari R.; Worsley L.; Allibone S.; Kasipandian V.; Patel A.; Cutting P.; Genetu R.; Mac A.; Murphy A.; Ward S.; Butt F.; Ayers A.; Harrison W.; Mackintosh K.; North J.; Ashton L.; Bi R.; Owen S.; Winmill H.; Scholefield B.; Blowing H.; Williams E.; Duskova M.; Edwards M.; Rees A.; Thomas H.; Hughes R.; Brooks J.; Phipps J.; Brooks S.; Dennis C.; Srikaran S.; Sukha A.; Tiongson G.; Adams K.; Andrew B.; Brayne A.; Carter S.; Findlay L.; Fisher E.; Jackson P.; Kaye D.; Parkin J.; Tuckey V.; Hunt J.; Love N.; van Koutrick L.; Hanson A.; Dent K.; Horsley E.; Pearson S.; Spencer S.; Hutchinson D.; Player J.; Potoczna D.; Akhtar M.N.; Cottam L.-J.; Nauyokas K.; Sanders J.; Garcia S.M.; Pakou G.; Diaba C.; Filipe H.; John L.; Maharajh A.; de Neef M.; Martin D.; Eastgate C.; Teoh P.C.; Barrett F.; Bradley C.; Donaldson A.; Mascarenhas M.; O'Hara M.; Okeefe L.; Clarke N.; Whiteside J.; Campbell R.; Matheson J.; McDonald D.; Patience D.; Rice P.; Smith T.; Clapham M.; Mutch R.; Barberis L.; Harper R.; Craig H.; Poultney U.; Burns K.; Higham A.; Twiss S.; Barton J.; George L.; Harrop C.; Mathew S.; Wright D.J.; Harrison R.; Toohie J.; Chandler B.; Turnbull A.; Mallinson J.; Elliott K.; Wolf-Roberts R.; Tench H.; Otahal I.; Hobrok M.; Loosley R.; McGuinness H.; Sims T.; Afolabi D.; Allison K.S.; Anderson T.; Dore R.; Jones D.; Rogers N.; Saunderson P.; Whitbread J.; O'Malley L.; Rad L.; Hawcutt D.; Aldridge J.; Tolson M.; Garrioch S.; Tomlinson J.; Grosdenier M.; Loader D.; Kapoor R.; Hector G.; Scherewode J.; Sri-Chandana C.; Stephenson L.; Marsh S.; Dela Rosa A.; Jhanji S.; Bemand T.; Howle R.; Baikady R.R.; Thomas B.; Black E.; Tatham K.; Gurram S.; Watson E.; Parris V.; Quaid S.; McGregor A.; Saunderson A.; O'Brien R.; Moultrie S.; Service J.; Cheyne C.; Odam M.; Wiliams A.; Barnes N.; Csabi P.; Da Rocha J.; Glynou L.; Huffenberger A.; Bryant J.; Pickard A.; Roe N.; Bellini A.; Mayer A.; Burrow A.; Colley N.; Evans J.; Howlett A.; Khalifeh Z.; Pryce J.; Gorman C.; Easthope A.; Brady R.; Timlick E.; Antoine P.; Gupta A.; Hardy J.; Houlden H.; Moncur E.; Tucci A.; Raith E.; Tariq A.; Brealey D.; Tagliavini E.; Ramsay B.; Fidler K.; Donnelly K.; Hollis R.; Barr J.; Boyd E.; Irvine V.; Shelley B.; Buckley J.; Hamilton C.; Valdeavella K.; Abellan J.; Acosta-Isaac R.; Aguado J.M.; Aguilar C.; Aguilera-Albesa S.; Sabbagh A.A.; Alba J.; Albu S.; Alcala-Gallardo K.A.M.; Alcoba-Florez J.; Batres S.A.; Algarin-Lara H.R.; Almadana V.; Almeida J.; Almoguera B.; Alonso M.R.; Alvarez N.; Alvarez-Benitez Y.; Alvarez-Navia F.; Walther R.A.-S.; Andreu-Bernabeu A.; Antonijoan M.R.; Arana-Arri E.; Aranda C.; Arango C.; Araque C.; Araujo N.K.; Araujo I.M.T.; Arcanjo A.C.; Arnaiz A.; Fernandez F.A.; Arranz M.J.; Lopez J.R.A.; Artiga M.-J.; Avello-Malaver Y.; Ayuso C.; Baldion A.M.; Martin B.B.; Baptista-Rosas R.C.; Barranco-Diaz A.; Barreda-Sanchez M.; Barrera-Penagos V.; Belhassen-Garcia M.; Bernal E.; Bernal-Bello D.; Bezerra J.F.; Bezerra M.A.C.; Blanca-Lopez N.; Blancas R.; Boix-Palop L.; Borobia A.; Bravo E.; Brion M.; Brochado-Kith O.; Brugada R.; Bustos M.; Cabello A.; Caceres-Agra J.J.; Calbo E.; Calderon E.J.; Camacho S.; Campos M.C.; Canadas Y.; Carbonell C.; Cardona-Huerta S.; Carioca A.A.F.; Carpintero M.S.; Segura C.C.; Carratto T.M.T.; Carrillo-Avila J.A.; Carvalho M.C.C.; Casasnovas C.; Castano L.; Castano C.F.; Castelao J.E.; Candalija A.C.; Castillo M.A.; Ceballos F.C.; Chaux J.G.; Chaves-Santiago W.G.; Chiquillo-Gomez S.; Cid-Lopez M.A.; Cienfuegos-Jimenez O.; Conde-Vicente R.; Cordero-Lorenzana M.L.; Corella D.; Corrales A.; Cortes-Sanchez J.L.; Corton M.; Costa T.X.; Cruz M.S.; Cuesta L.; Cunha G.C.R.; da Silva G.V.; Dalmau D.; Dantas-Komatsu R.C.S.; Darnaude M.T.; de Andres R.; de Araujo J.N.G.; de Juan C.; De la Cruz Troca J.; de la Horra C.; de la Hoz A.B.; De Martino-Rodriguez A.; de Sousa Alves Neri J.L.; del Campo-Perez V.; Delgado-Cuesta J.; Diaz-Caneja C.M.; Diaz-Perez A.; de Bustamante A.D.; Dietl B.; Diz-de Almeida S.; Alves M.M.; Dominguez-Garrido E.; dos Santos K.A.; Duarte A.M.; Echave-Sustaeta J.; Eiros R.; Enciso-Olivera C.O.; Escudero G.; Espana P.P.; Sanabria G.M.E.; Farinas M.C.; Fernandes M.R.; Fernandez R.; Fernandez-Caballero L.; Fernandez-Cruz A.; Fernandez-Nestosa M.J.; Fernandez-Robelo U.; Fernandez-Rodriguez A.; Fernandez-Sampedro M.; Fernandez-Sanchez R.; Fernandez-Villa T.; Ferrero S.F.; Martinez Y.F.; Capitan C.F.; Flores-Perez P.; Friaza V.; Fuenmayor-Hernandez L.; Nunez M.F.; Fumado V.; Gadea I.; Gagliardi L.; Gago-Dominguez M.; Gallego N.; Galoppo C.; Garcia I.; Garcia M.; Garcia L.; Garcia-Cerrada C.; Garcia-de-Vicuna A.; Garcia-Garcia J.; Garcia-Garcia I.; Garcia-Ibarbia C.; Garcia-Montero A.C.; Garcia-Soidan A.; Garcia-Vazquez E.; Torrejon M.C.G.; Garza-Frias E.; Gentile A.; Gil-Fournier B.; Gomez-Arrue J.; Gomez-Duque M.; Carrera L.G.; Garcia M.G.; Sacristan A.G.; Gonzalez-Neira A.; Gonzalez-Penas J.; Gonzalez-Sagrado M.; Alvarez B.G.; de Quiros F.G.B.; Benito H.G.; Gorgojo-Galindo O.; Gorgolas M.; Guaragna F.; Guegel G.P.; Guillen-Guio B.; Guillen-Navarro E.; Guisado-Vasco P.; Gutierrez-Bautista J.F.; Gutierrez-Castaneda L.D.; Heili-Frades S.; Hernandez E.; Hernandez-Ortega L.D.; Hernandez-Perez G.; Hernandez-Vaquero R.; Moro C.H.; Herraez B.; Herranz M.T.; Herrera M.; Herrero M.J.; Herrero-Gonzalez A.; Horcajada J.P.; Imaz-Ayo N.; Intxausti-Urrutibeaskoa M.; Iniguez M.; Jacomo R.H.; Jara R.; Jazmin P.M.; Jimenez A.; Jimenez P.; Jimenez-Alfaro I.; Jimenez-Sousa M.A.; Jordan I.; Laguna-Goya R.; Laorden D.; Lasa-Lazaro M.; Lattig M.C.; Lauriente A.; Borja A.L.; Llanos L.; Lopez-Bernus A.; Lopez-Garcia E.; Lopez-Rodriguez R.; Lopez-Ruz M.A.; Granados E.L.; Lorente L.; Lozano J.E.; Lozano-Espinosa M.; Mahillo I.; Mancebo E.; Mar C.; Calvo C.M.; Marcos M.; Marcos-Delgado A.; Candon A.M.; Aguilar P.M.; Martin M.M.; Martin M.D.; Martin V.; Martin-Fernandez M.; Martin-Lopez C.; Martin-Oterino J.-A.; Martin-Pedraza L.; Martin-Vicente M.; Martinez A.; Martinez R.; Martinez J.J.; Martinez S.; Martinez-Aquino E.; Martinez-Gonzalez O.; Martinez-Lopez I.; Martinez-Nieto O.; Martinez-Paz P.; Martinez-Perez A.; Martinez-Ramas A.; Martinez-Resendez M.F.; Robles V.M.; Marzal L.; Mazzeu J.F.; Medeiros J.F.P.; Medeiros K.A.; Medrano F.J.; Meijome X.M.; Mejuto-Montero N.; Mendez-Echevarria A.; Charris H.M.; Macias E.M.; Mercadillo F.; Mercado-Sesma A.R.; Minguez P.; Molina A.J.J.; Molina-Roldan E.; Montoya J.J.; Moraes V.M.S.; Moreira-Escriche P.; Morelos-Arnedo X.; Moreno-Docon A.; Moreno-Escalante J.; Cuerda V.M.; Fernandez A.M.; Morilla R.; Garcia P.M.; Neira P.; Nevado J.; Nieto-Ganan I.; Nunes J.F.R.; Nunez-Torres R.; Obrador-Hevia A.; Ocejo-Vinyals J.G.; Olivar V.; Oliveira S.F.; Ondo L.; Orfao A.; Ortega L.; Ortega-Paino E.; Ortiz-Flores F.; Ortiz-Lopez R.; Oteo J.A.; Pachajoa H.; Pacheco M.; Pacheco-Miranda F.J.; Conejo I.P.; Panadero-Fajardo S.; Parellada M.; Pariente-Rodriguez R.; Paz-Artal E.; Peces-Barba G.; Pedromingo Kus M.S.; Perales C.; Perez P.; Perez C.; Perez-de-Nanclares G.; Perez-Garcia F.; Perez-Matute P.; Perez-Serra A.; Perez-Tomas M.E.; Perucho T.; Pichardo L.A.; Pinho S.M.T.; Pinsach-Abuin M.; Pinzon L.A.; Pita G.; Pla-Junca F.; Planas-Serra L.; Pompa-Mera E.N.; Porras-Hurtado G.L.; Pujol A.; Chavez M.E.Q.; Quijada M.A.; Quintela I.; Ramirez-Montano D.; Leon S.R.; Sedes P.R.; Recalde D.; Recio-Fernandez E.; Resino S.; Ribeiro A.P.; Rivadeneira-Chamorro C.S.; Roa-Agudelo D.; Pardo M.R.; Rodriguez M.J.; Rodriguez-Artalejo F.; Rodriguez-Ferrer M.; Rodriguez-Gallego C.; Rodriguez-Garcia J.A.; Rodriguez-Hernandez M.A.; Rodriguez-Nicolas A.; Rodriguez-Palmero A.; Rodriguez-Ruiz E.; Rodriguez-Urrego P.A.; Maya B.R.; Novoa G.E.R.; Rojo F.; Romero-Coronado A.; Garcia F.R.; Rosa L.S.; Rosales-Castillo A.; Rubio C.; Olivera M.R.; Ruiz M.; Ruiz-Cabello F.; Ruiz-Casares E.; Ruiz-Cubillan J.J.; Ruiz-Hornillos J.; Ryan P.; Salamanca H.D.; Salazar-Garcia L.; Origlia G.G.S.; Sanchez P.-L.; Sanchez-Pablo C.; Sanchez-Pernaute O.; Sanchez Lopez A.J.; Prados M.C.S.; Real J.S.; Redondo J.S.; Sancho-Sainz C.; Sangil A.; Santos A.; Santos N.P.C.; Schluter A.; Segovia S.; Serra-Llovich A.; Puras F.S.; Porras M.S.; Sicolo M.A.; Silbiger V.N.; Silva N.S.; Silva F.T.C.; Fuentes C.S.; Sole-Violan J.; Soria J.M.; Sorli J.V.; Sousa R.R.; Souto J.C.; Souza K.S.C.; Souza V.S.; Sprockel J.J.; Suarez-Rama J.J.; Suarez-Zamora D.A.; Taboada-Fraga X.; Tamayo E.; Tamayo-Velasco A.; Taracido-Fernandez J.C.; Tavares N.A.C.; Telleria C.; Castano J.A.T.; Teper A.; Torres-Macho J.; Torres-Tobar L.; Torres Gutierrez R.P.; Troya J.; Urioste M.; Valencia-Ramos J.; Valido A.; Gallo J.P.V.; Varon B.; Vasconcelos R.H.T.; Vega T.; Velasco-Quirce S.; Velez-Santamaria V.; Victor V.; Estevez J.V.; Vieitez-Santiago M.; Vilches C.; Villalobos L.; Villar F.; Villar-Garcia J.; Villaverde C.; Villoslada-Blanco P.; Virseda-Berdices A.; Yanez Z.; Zapatero-Gaviria A.; Zarate R.; Zazo S.; de Heredia M.L.; Mendes I.; Moreno R.; Sande E.; Lapunzina P.; Alex B.; Andrikopoulos P.; Bach B.; Barclay W.S.; Bogaert D.; Chand M.; Chechi K.; Cooke G.S.; da Silva Filipe A.; de Silva T.; Docherty A.B.; dos Santos Correia G.; Dumas M.-E.; Dunning J.; Fletcher T.; Green C.A.; Greenhalf W.; Griffin J.; Gupta R.K.; Harrison E.M.; Ho A.Y.W.; Holden K.; Horby P.W.; Ijaz S.; Khoo S.; Klenerman P.; Lewis M.; Liggi S.; Lim W.S.; Maslen L.; Mentzer A.J.; Merson L.; Meynert A.M.; Moore S.C.; Noursadeghi M.; Olanipekun M.; Osagie A.; Palmarini M.; Palmieri C.; Paxton W.A.; Pollakis G.; Price N.; Rambaut A.; Robertson D.L.; Russell C.D.; Sancho-Shimizu V.; Sands C.; Scott J.T.; Sigfrid L.; Solomon T.; Sriskandan S.; Stuart D.; Swann O.V.; Takats Z.; Takis P.; Tedder R.S.; Thompson A.A.R.; Thomson E.C.; Thwaites R.S.; Turtle L.C.W.; Zambon M.; Carson G.; Drake T.M.; Fairfield C.J.; Knight S.R.; Mclean K.A.; Murphy D.; Norman L.; Pius R.; Shaw C.A.; Connor M.; Dalton J.; Gamble C.; Girvan M.; Halpin S.; Harrison J.; Jackson C.; Marsh L.; Roberts S.; Saviciute E.; Knight S.; Lahnsteiner E.; Leeming G.; Norris L.; Scott-Brown J.; Tait S.; Wham M.; Lee J.; Plotkin D.; Keating S.; Donegan C.; Spencer R.G.; Donohue C.; Hardwick H.; Shelton J.F.; Shastri A.J.; Ye C.; Weldon C.H.; Filshtein-Sonmez T.; Coker D.; Symons A.; Esparza-Gordillo J.; Aslibekyan S.; Auton A.; Yang J.; Ponting C.P.; Wilson J.F.; Vitart V.; Abedalthagafi M.; Luchessi A.D.; Parra E.J.; Cruz R.; Carracedo A.; Fawkes A.; Murphy L.; Rowan K.; Pereira A.C.; Law A.; Fairfax B.; Hendry S.C.; Baillie J.K.

Citation:
Nature. 617(7962) (pp 764-768), 2023. Date of Publication: 25 May 2023.

Abstract:
Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown<sup>1</sup> to be highly efficient for discovery of genetic associations<sup>2</sup>. 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 group<sup>3</sup>. 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).

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The Impact of Artificial Intelligence on Optimizing Diagnosis and Treatment Plans for Rare Genetic Disorders (2023)

Type of publication:Journal article

Author(s):Abdallah, Shenouda; Sharifa, Mouhammad; I Kh Almadhoun, Mohammed Khaleel; Khawar, Muhammad Muneeb Sr; Shaikh, Unzla; Balabel, Khaled M; Saleh, Inam; Manzoor, Amima; Mandal, Arun Kumar; *Ekomwereren, Osatohanmwen; Khine, Wai Mon; Oyelaja, Oluwaseyi T.

Citation:Cureus. 15(10):e46860, 2023 Oct.

Abstract:Rare genetic disorders (RDs), characterized by their low prevalence and diagnostic complexities, present significant challenges to healthcare systems. This article explores the transformative impact of artificial intelligence (AI) and machine learning (ML) in addressing these challenges. It emphasizes the need for accurate and early diagnosis of RDs, often hindered by genetic and clinical heterogeneity. This article discusses how AI and ML are reshaping healthcare, providing examples of their effectiveness in disease diagnosis, prognosis, image analysis, and drug repurposing. It highlights AI's ability to efficiently analyze extensive datasets and expedite diagnosis, showcasing case studies like Face2Gene. Furthermore, the article explores how AI tailors treatment plans for RDs, leveraging ML and deep learning (DL) to create personalized therapeutic regimens. It emphasizes AI's role in drug discovery, including the identification of potential candidates for rare disease treatments. Challenges and limitations related to AI in healthcare, including ethical, legal, technical, and human aspects, are addressed. This article underscores the importance of data ethics, privacy, and algorithmic fairness, as well as the need for standardized evaluation techniques and transparency in AI research. It highlights second-generation AI systems that prioritize patient-centric care, efficient patient recruitment for clinical trials, and the significance of high-quality data. The integration of AI with telemedicine, the growth of health databases, and the potential for personalized therapeutic recommendations are identified as promising directions for the field. In summary, this article provides a comprehensive exploration of how AI and ML are revolutionizing the diagnosis and treatment of RDs, addressing challenges while considering ethical implications in this rapidly evolving healthcare landscape.

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Improving the Outcome of Patients With Heart Failure: Assessment of Iron Deficiency and Intravenous Iron Replacement (2023)

Type of publication:Journal article

Author(s):*Yera, Hassan O; Khan, Ahsan; Akinlade, Olawale M; Champsi, Asgher; Glouzon, Van Nam J; Spencer, Charles.

Citation:Cureus. 15(10):e47027, 2023 Oct.

Abstract:Background Iron deficiency (ID) has been shown to be a significant co-morbidity in patients with heart failure (HF), independent of their anaemia status. Correction of ID has been shown to improve quality of life, recurrent heart failure hospitalizations and morbidity. A quality improvement project was designed to improve the assessment and treatment of iron deficiency in HFatients in our tertiary care centre. Methods and results An initial baseline dataset was collected, followed by two cycles of interventions to help improve the care of HF patients admitted to our hospital over a two-month period. The Plan-Do-Study-Act (PDSA) cycle approach was applied, with the first intervention involving raising awareness of the importance and need to assess the iron status of HF patients through education provided to doctors, nurses and patients. Furthermore, information leaflets were produced and disseminated across the medical wards and through social media forums. The post-intervention datasets were collected and compared to the baseline outcomes. Baseline data showed that only four (20%) of heart failure patients had their iron status checked. Following the interventions, screening for ID increased to 80% (16), of which 85% (11) of those who identified as iron deficient received intravenous iron replacement. Conclusion The project was successful in improving the practice of screening for iron deficiency and intravenous replacement of iron in patients with HF.

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The development and acceptability of an educational and training intervention for recruiters to neonatal trials: the TRAIN project (2023)

Type of publication:Journal article

Author(s):Smith, V; Delaney, H; Hunter, A; Torgerson, D; Treweek, S; Gamble, C; Mills, N; Stanbury, K; Dempsey, E; Daly, M; O'Shea, J; Weatherup, K; *Deshpande, S; Ryan, M A; Lowe, J; Black, G; Devane, D.

Citation:BMC Medical Research Methodology. 23(1):265, 2023 Nov 11.

Abstract:BACKGROUND: Suboptimal or slow recruitment affects 30-50% of trials. Education and training of trial recruiters has been identified as one strategy for potentially boosting recruitment to randomised controlled trials (hereafter referred to as trials). The Training tRial recruiters, An educational INtervention (TRAIN) project was established to develop and assess the acceptability of an education and training intervention for recruiters to neonatal trials. In this paper, we report the development and acceptability of TRAIN. METHODS: TRAIN involved three sequential phases, with each phase contributing information to the subsequent phase(s). These phases were 1) evidence synthesis (systematic review of the effectiveness of training interventions and a content analysis of the format, content, and delivery of identified interventions), 2) intervention development using a Partnership (co-design/co-creation) approach, and 3) intervention acceptability assessments with recruiters to neonatal trials. RESULTS: TRAIN, accompanied by a comprehensive intervention manual, has been designed for online or in-person delivery. TRAIN can be offered to recruiters before trial recruitment begins or as refresher sessions during a trial. The intervention consists of five core learning outcomes which are addressed across three core training units. These units are the trial protocol (Unit 1, 50 min, trial-specific), understanding randomisation (Unit 2, 5 min, trial-generic) and approaching and engaging with parents (Unit 3, 70 min, trial-generic). Eleven recruiters to neonatal trials registered to attend the acceptability assessment training workshops, although only four took part. All four positively valued the training Units and resources for increasing recruiter preparedness, knowledge, and confidence. More flexibility in how the training is facilitated, however, was noted (e.g., training divided across two workshops of shorter duration). Units 2 and 3 were considered beneficial to incorporate into Good Clinical Practice Training or as part of induction training for new staff joining neonatal units. CONCLUSION: TRAIN offers a comprehensive co-produced training and education intervention for recruiters to neonatal trials. TRAIN was deemed acceptable, with minor modification, to neonatal trial recruiters. The small number of recruiters taking part in the acceptability assessment is a limitation. Scale-up of TRAIN with formal piloting and testing foreffectiveness in a large cluster randomised trial is required.

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A study analyzing the clinical, histopathological and immunological profile of patients with cutaneous vasculitis: IgA vasculitis and IgA-negative vasculitis (2023)

Type of publication:Journal article

Author(s):Kakroo S.N.; Khan M.A.; Beg M.A.; *Kakroo B.

Citation:Journal of Pakistan Association of Dermatologists. 33(4) (pp 1562-1568), 2023. Date of Publication: October 2023.

Abstract:Background Skin is frequently involved in small-vessel vasculitis. Based on immunofluorescence studies, it can be IgA type (Henoch-Schoenlein purpura) or IgA-negative type i.e. leukocytoclastic vasculitis. Clinically, palpable purpura is the hallmark of the disease. Both subtypes can be associated with variable systemic involvement. Objective To compare the clinical, histopathological and immunological profile of patients with IgA and IgA-negative vasculitis with special reference to renal involvement. Methods Seventy-five patients presenting to the outpatient clinic of a tertiary care hospital with a clinical diagnosis of palpable purpura were enrolled in the study. All patients had a thorough clinical examination and detailed history, and results were documented on a pre-made proforma. Results On direct immunofluorescence findings, 40 patients had IgA vasculitis and 35 IgA-negative vasculitis. The mean age of presentation was 38.8 years in IgA vasculitis and 54.3 years in IgA-negative vasculitis. IgA vasculitis presented with frequent cutaneous (n=27, 67.5%, itching or pain) and systemic symptoms (n=18, 45%, abdominal and joints) seventeen (42.5%) as compared to IgA-negative subgroup (25.4% and 11.4%, respectively). Morphologically, palpable purpura was seen in both groups, but 11.4% patients in IgA-negative vasculitis group presented with ulcerated lesions. Patients of both groups had vessel wall fibrin deposition and necrosis, inflammatory infiltrate in the vessel wall, erythrocyte extravasation, unclear dust and endothelial swelling in descending frequencies. Complement 3 (C3) was the commonest immunoreactant (n=71; 94.7%) followed by fibrinogen (n=59; 78.7%) and immunoglobulin A (IgA) [n=40; 53.3%]. Abnormal urine microscopy findings were detected in (n=28; 70%) patients with IgA vasculitis and in (n=2; 5.7%) with IgA-negative vasculitis. Serum creatinine was raised in 12 (30%) patients with IgA vasculitis and 7 (20%) patients with IgA-negative vasculitis. Other laboratory tests had similar frequency in two groups. Conclusion IgA vasculitis was seen in a relatively younger age group in comparison to IgA-negative vasculitis. C3 was the commonest immunoreactant staining the blood vessel wall followed by fibrinogen and IgA. Renal involvement occurred more frequently in the IgA vasculitis.

P2.23-07 Crucial, Complex, Caring: A Professional Development Framework for Lung Cancer Nurse Specialists (2023)

Type of publication:Conference abstract

Author(s):Clayton K.J.; Fenemore J.; Barton P.; Roberts J.; Ivey S.; *McAdam J.; Shepherd P.; Magee L.

Citation:Journal of Thoracic Oncology. Conference: 2023 World Conference on Lung Cancer. Singapore Singapore. 18(11 Supplement) (pp S397), 2023. Date of Publication: November 2023.

Abstract:Introduction: Lung cancer specialist nursing is a varied, valuable and rewarding career, and the need for lung cancer nurse specialists (LCNS) is increasing. Lung Cancer Nursing UK (LCNUK) wants to encourage nurses to aspire to becoming an LCNS, and to support those already working in lung cancer teams to flourish professionally. We want employers to recognise LCNS' capabilities and to recruit and reward them accordingly. LCNUK therefore set out to draft the first professional development framework for LCNS. The Framework is intended to guide nurses, line managers and employers on the core skills, knowledge and expertise that LCNS will gain and demonstrate as they progress in role. Method(s): LCNUK convened a working group which reviewed exemplars and supporting literature., aligned with the four pillars of advanced practice. Feedback on the draft was sought from expert stakeholders and was approved by the LCNUK Steering Committee. The Framework was developed in a collaboration between LCNUK and MSD, who funded a policy consultancy to provide support. LCNUK retained editorial independence. Result(s): The Framework sets out the qualifications, clinical skills, knowledge, leadership and management and research capabilities that LCNUK expects aspiring and existing LCNS to demonstrate or be working towards. It includes case studies of nurses' career journeys and an example of a successful case for job matching and re-banding. The Framework is available on the LCNUK website at. Conclusion(s): The Framework asserts the crucial role of LCNS in managing safety-critical and complex patient care and in leading service delivery and improvement. We hope it will prove a valuable tool to nurses, employers and policymakers in understanding the complexity and importance of this essential role. Following collaboration with European lung cancer nursing colleagues, via ELCC 2022, while not implemented the value and importance of the framework has been acknowledged by Croatian colleagues.The framework has also been welcomed and acknowledged by the devolved nations of the United Kingdom, Wales, Scotland and Northern Ireland.

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Setting up a Complex Abdominal Wall Reconstruction Unit: Our first 12 months' experience in a District General Hospital (2023)

Type of publication:Conference abstract

Author(s):*Bhandari M.; *George J.; *Chakravartty S.; *Parampalli U.; *McCloud J.; *Cheetham M.

Citation:British Journal of Surgery. Conference: Annual Congress of the Association of Surgeons of Great Britain and Ireland. Harrogate United Kingdom. 110(Supplement 6) (pp vi50-vi51), 2023.

Abstract:Aims: Incisional hernias are distressing post-operative complications which develop in 25% of surgical incisions. We present our initial experience of setting up a Complex Abdominal Wall Reconstruction (CAWR) unit in line with international guidelines and Get It Right First Time (GIRFT) model of care. Method(s): A bespoke CAWR Multidisciplinary Team was established in our trust in January 2022, comprising 2 colorectal surgeons, 2 bariatric surgeons and anaesthetists (who performed the preoperative Botox injections and optimized high-risk patients). The unit had support from radiologists, the weight management service, and the orthotics department. We had approval from our governance, drugs and therapeutics team. Pathways for risk stratification, risk modification with pre-optimisation, standardised surgical techniques and post-operative care were created. Result(s): Between January and December 2022, 8 MDT meetings held and 52 patients were discussed. The average BMI was 34 (22-50.5) All patients underwent a preoperative CT scan to delineate the anatomy of the hernia. The median size of the defect was 6 cm (range 3 to 22 cm). Open Rives-Stoppa repair was performed in 19 patients, with transversus abdominal muscle release in 6 and 3 patients had laparoscopic repair. One recurrence and 2 superficial surgical site infections were noted. 38.4% patients had BOTOX, 40.3% advised preoperative weight loss and 5.7% for bariatric surgery before hernia repair. A high-risk anaesthetic opinion was obtained in for 7.6% and 17% were deemed unfit. Conclusion(s): Our initial experience and data highlight the feasibility of delivery of CAWR service at a non-tertiary unit in line with GIRFT principles. The initial follow-up indicates improved patient outcomes and experience.

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Saving inpatient beds: are day-case total parathyroidectomies possible and safe? (2023)

Type of publication:Conference abstract

Author(s):*Sultana E.; *McDonald S.; Al-Saadi N.; Chang J.; *Sandhu K.; *Houghton A.

Citation:British Journal of Surgery. Conference: Annual Congress of the Association of Surgeons of Great Britain and Ireland. Harrogate United Kingdom. 110(Supplement 6) (pp vi12), 2023.

Abstract:Introduction: Total parathyroidectomy on patients with hyperparathyroidism traditionally required an inpatient hospital stay to monitor patients for postoperative hypocalcaemia. Our centre developed a safe protocol in 2015 which enables total parathyroidectomies to be carried out as a day-case procedure. This protocol, developed in conjunction with the renal physicians, involves giving the patient oral alfacalcidol preoperatively for 5 days and close monitoring of the calcium levels postoperatively to permit safe same day discharge. Method(s): A single centre retrospective study was carried out on all patients who underwent a total parathyroidectomy for hyperparathyroidism between 2005 and 2022. A comparison study was done before and after the protocol was introduced in 2015. Data were collected regarding the patient comorbidities, peri-operative calcium level, post-operative calcium, potassium and parathyroid levels, length of hospital stay, operative procedure details, hospital readmission, and 30-day morbidity. Result(s): 57 patients underwent total parathyroidectomy during the study period (22 before protocol and 35 after the protocol). After introduction of the protocol, 40% of patients were discharged on the same day, compared to only 4.54% previously. The duration of inpatient hospital stay was reduced from 0-13 days to 0-3 days. Reasons for prolonged hospital stay in the remaining patients included refractory hyperkalaemia requiring dialysis, complications secondary to anaesthesia, as well as hypocalcaemia in a few cases. No patient required readmission during the 30-day post-operative period. Conclusion(s): Day-case surgery for total parathyroidectomy can be achieved safely in patients with a preoperative regimen of alfacalcidol and close monitoring of calcium levels post-operatively, emulating a virtual ward round.

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Predictors of mortality in periprosthetic fractures of the hip: results from the national PPF study (2023)

Type of publication:Journal article

Author(s):Nasser, Ahmed Abdul Hadi Harb; Prakash, Rohan; Handford, Charles; Osman, Khabab; Chauhan, Govind Singh; Nandra, Rajpal; Mahmood, Ansar; Dewan, Varun; Davidson, Jerome; Al-Azzawi, Mohammed; Smith, Christian; Gawad, Mothana; Palaiologos, Ioannis; Cuthbert, Rory; Wignadasan, Warran; Banks, Daniel; Archer, James; Odeh, Abdulrahman; Moores, Thomas; Tahir, Muaaz; Brooks, Margaret; Biring, Gurdeep; Jordan, Stevan; Elahi, Zain; Shaath, Mohammed; Veettil, Manoj; De, Chiranjit; Handford, Charles; Bansal, Mohit; Bawa, Akshdeep; Mattar, Ahmed; Tandra, Varun; Daadipour, Audrina; Taha, Ahmed; Gangoo, Shafat; Srinivasan, Sriram; Tarisai, Mandishona; Budair, Basil; Subbaraman, Krishna; Khan, Farrukh; Gomindes, Austin; Samuel, Arjun; Kang, Niel; Kapur, Karan; Mainwaring, Elizabeth; Bridgwater, Hannah; Lo, Andre; Ahmed, *Usman; Khaleeq, *Tahir; El-Bakoury, Ahmed; Rashed, Ramy; Hosny, Hazem; Yarlagadda, Rathan; Keenan, Jonathan; Hamed, Ahmed; Riemer, Bryan; Qureshi, Arham; Gupta, Vatsal; Waites, Matthew; Bleibleh, Sabri; Westacott, David; Phillips, Jonathan; East, Jamie; Huntley, Daniel; Masud, Saqib; Mirza, Yusuf; Mishra, Sandeep; Dunlop, David; Khalefa, Mohamed; Balasubramanian, Balakumar; Thibbaiah, Mahesh; Payton, Olivia; Berstock, James; Deano, Krisna; Sarraf, Khaled; Logishetty, Kartik; Lee, George; Subbiah-Ponniah, Hariharan; Shah, Nirav; Venkatesan, Aakaash; Cheseldene-Culley, James; Ayathamattam, Joseph; Tross, Samantha; Randhawa, Sukhwinder; Mohammed, Faisal; Ali, Ramla; Bird, Jonathan; Khan, Kursheed; Akhtar, Muhammad Adeel; Brunt, Andrew; Roupakiotis, Panagiotis; Subramanian, Padmanabhan; Bua, Nelson; Hakimi, Mounir; Bitar, Samer; Najjar, Majed Al; Radhakrishnan, Ajay; Gamble, Charlie; James, Andrew; Gilmore, Catherine; Dawson, Dan; Sofat, Rajesh; Antar, Mohamed; Raghu, Aashish; Heaton, Sam; Tawfeek, Waleed; Charles, Christerlyn; Burnand, Henry; Duffy, Sean; Taylor, Luke; Magill, Laura; Perry, Rita; Pettitt, Michala; Okoth, Kelvin; Pinkney, Thomas.

Citation:Injury. 54(12):111152, 2023 Oct 24.

Abstract:INTRODUCTION: Periprosthetic fractures (PPFs) around the hip joint are increasing in prevalence. In this collaborative study, we aimed to investigate the impact of patient demographics, fracture characteristics, and modes of management on in-hospital mortality of PPFs involving the hip. METHODS: Using a multi-centre cohort study design, we retrospectively identified adults presenting with a PPF around the hip over a 10-year period. Univariate and multivariable logistic regression analyses were performed to study the independent correlation between patient, fracture, and treatment factors on mortality. RESULTS: A total of 1,109 patients were included. The in-hospital mortality rate was 5.3%. Multivariable analyses suggested that age, male sex, abbreviated mental test score (AMTS), pneumonia, renal failure, history of peripheral vascular disease (PVD) and deep surgical site infection were each independently associated with mortality. Each yearly increase in age independently correlates with a 7% increase in mortality (OR 1.07, p=0.019). The odds of mortality was 2.99 times higher for patients diagnosed with pneumonia during their hospital stay [OR 2.99 (95% CI 1.07-8.37) p=0.037], and 7.25 times higher for patients that developed renal failure during their stay [OR 7.25 (95% CI 1.85-28.47) p=0.005]. Patients with history of PVD have a six-fold greater mortality risk (OR 6.06, p=0.003). Mode of treatment was not a significant predictor of mortality. CONCLUSION: The in-hospital mortality rate of PPFs around the hip exceeds 5%. The fracture subtype and mode of management are not independent predictors of mortality, while patient factors such as age, AMTS, history of PVD, pneumonia, and renal failure can independently predict mortality. Peri-operative optimisation of modifiable risk factors such as lung and kidney function in patients with PPFs around the hip during their hospital stay is of utmost importance.

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