Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus
Timothy R D J Radstake,Olga Y. Gorlova,Blanca Rueda,Jose Ezequiel Martin,Behrooz Z. Alizadeh,Rogelio Palomino-Morales,Marieke J H Coenen,Madelon C. Vonk,Alexandre E. Voskuyl,Annemie J. Schuerwegh,Jasper C A Broen,Piet L. C. M. van Riel,Ruben van 't Slot,Annet Italiaander,Roel A. Ophoff,Roel A. Ophoff,Gabriela Riemekasten,Nico Hunzelmann,Carmen P. Simeon,Norberto Ortego-Centeno,Miguel A. Gonzalez-Gay,María Francisca González-Escribano,Paolo Airò,Jaap M van Laar,Ariane L. Herrick,Jane Worthington,Roger Hesselstrand,Vanessa Smith,Filip De Keyser,Fredric Houssiau,Meng May Chee,Rajan Madhok,Paul G. Shiels,Rene Westhovens,Alexander Kreuter,Hans P. Kiener,Elfride De Baere,Torsten Witte,Leonid Padykov,Lars Klareskog,Lorenzo Beretta,Rafaella Scorza,Benedicte A. Lie,Anna Maria Hoffmann-Vold,Patricia Carreira,John Varga,Monique Hinchcliff,Peter K. Gregersen,Annette Lee,Jun Ying,Younghun Han,Shih-Feng Weng,Christopher I. Amos,Fredrick M. Wigley,Laura K. Hummers,J. Lee Nelson,Sandeep K. Agarwal,Shervin Assassi,Pravitt Gourh,Filemon K. Tan,Bobby P. C. Koeleman,Frank C. Arnett,Javier Martín,Maureen D. Mayes +63 more
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The first genome-wide association study in a population of European ancestry including a total of 2,296 individuals with SSc and 5,171 controls identified a new susceptibility locus for systemic sclerosis at CD247 (1q22–23, rs2056626).Abstract:
Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs that leads to profound disability and premature death. To identify new SSc susceptibility loci, we conducted the first genome-wide association study in a population of European ancestry including a total of 2,296 individuals with SSc and 5,171 controls. Analysis of 279,621 autosomal SNPs followed by replication testing in an independent case-control set of European ancestry (2,753 individuals with SSc (cases) and 4,569 controls) identified a new susceptibility locus for systemic sclerosis at CD247 (1q22-23, rs2056626, P = 2.09 x 10(-7) in the discovery samples, P = 3.39 x 10(-9) in the combined analysis). Additionally, we confirm and firmly establish the role of the MHC (P = 2.31 x 10(-18)), IRF5 (P = 1.86 x 10(-13)) and STAT4 (P = 3.37 x 10(-9)) gene regions as SSc genetic risk factors.read more
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JAK and STAT Signaling Molecules in Immunoregulation and Immune-Mediated Disease
TL;DR: Not only have genome-wide association studies demonstrated that this pathway is highly relevant to human autoimmunity, but targeting JAKs is now a reality in immune-mediated disease.
Journal ArticleDOI
Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens
Krzysztof Kiryluk,Yifu Li,Francesco Scolari,Simone Sanna-Cherchi,Murim Choi,Miguel Verbitsky,David Fasel,Sneh Lata,Sindhuri Prakash,Samantha Shapiro,Clara Fischman,Holly J. Snyder,Gerald B. Appel,Claudia Izzi,Battista Fabio Viola,Nadia Dallera,Lucia Del Vecchio,Cristina Barlassina,Erika Salvi,Francesca Bertinetto,Antonio Amoroso,Silvana Savoldi,Marcella Rocchietti,Alessandro Amore,Licia Peruzzi,Rosanna Coppo,Maurizio Salvadori,Pietro Ravani,Riccardo Magistroni,Gian Marco Ghiggeri,Gianluca Caridi,Monica Bodria,Francesca Lugani,Landino Allegri,Marco Delsante,Mariarosa Maiorana,Andrea Magnano,Giovanni M. Frascà,Emanuela Boer,Giuliano Boscutti,Claudio Ponticelli,Renzo Mignani,Carmelita Marcantoni,Domenico Di Landro,Domenico Santoro,Antonello Pani,Rosaria Polci,Sandro Feriozzi,Silvana Chicca,Marco Galliani,Maddalena Gigante,Loreto Gesualdo,Pasquale Zamboli,Giovanni Giorgio Battaglia,Maurizio Garozzo,Dita Maixnerova,Vladimir Tesar,Frank Eitner,Thomas Rauen,Jürgen Floege,Tibor Kovács,Judit Nagy,Krzysztof Mucha,Leszek Pączek,Marcin Zaniew,Małgorzata Mizerska-Wasiak,Maria Roszkowska-Blaim,Krzysztof Pawlaczyk,Daniel P. Gale,Jonathan Barratt,Lise Thibaudin,François Berthoux,Guillaume Canaud,Anne Boland,Marie Metzger,Ulf Panzer,Hitoshi Suzuki,Shin Goto,Ichiei Narita,Yasar Caliskan,Jingyuan Xie,Ping Hou,Nan Chen,Hong Zhang,Robert J. Wyatt,Jan Novak,Bruce A. Julian,John Feehally,Bénédicte Stengel,Daniele Cusi,Richard P. Lifton,Ali G. Gharavi +91 more
TL;DR: A genome-wide association study of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry is performed, suggesting a possible role for host–intestinal pathogen interactions in shaping the genetic landscape of IgAN.
Journal ArticleDOI
Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjogren's syndrome.
Christopher J. Lessard,Christopher J. Lessard,He Li,He Li,Indra Adrianto,John A. Ice,Astrid Rasmussen,Kiely Grundahl,Jennifer A. Kelly,Mikhail G. Dozmorov,Corinne Miceli-Richard,Simon J. Bowman,Susan C. Lester,Per Eriksson,Maija-Leena Eloranta,Johan G. Brun,Lasse G. Gøransson,Erna Harboe,Joel M. Guthridge,Kenneth M. Kaufman,Kenneth M. Kaufman,Marika Kvarnström,Helmi Jazebi,Helmi Jazebi,Deborah S. Cunninghame Graham,Martha E. Grandits,Abu N. M. Nazmul-Hossain,Ketan Patel,Adam Adler,Jacen S. Maier-Moore,Jacen S. Maier-Moore,A. Darise Farris,Michael T. Brennan,James A. Lessard,James Chodosh,Rajaram Gopalakrishnan,Kimberly S. Hefner,Glen D Houston,Andrew J.W. Huang,Pamela J. Hughes,David M Lewis,Lida Radfar,Michael D. Rohrer,Donald U. Stone,Jonathan D. Wren,Timothy J. Vyse,Patrick M. Gaffney,Judith A. James,Judith A. James,Roald Omdal,Marie Wahren-Herlenius,Gabor G. Illei,Torsten Witte,Roland Jonsson,Maureen Rischmueller,Lars Rönnblom,Gunnel Nordmark,Wan-Fai Ng,Xavier Mariette,Juan-Manuel Anaya,Nelson L. Rhodus,Barbara M. Segal,R. Hal Scofield,Courtney G. Montgomery,John B. Harley,John B. Harley,Kathy L. Sivils,Kathy L. Sivils +67 more
TL;DR: The results highlight the importance of genes that are involved in both innate and adaptive immunity in Sjögren's syndrome, including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2 and PHIP, among others.
Journal ArticleDOI
Proteome-wide Analysis and CXCL4 as a Biomarker in Systemic Sclerosis
L. van Bon,L. van Bon,Alsya J. Affandi,Alsya J. Affandi,J. Broen,J. Broen,Romy B. Christmann,Renoud J. Marijnissen,Lukasz Stawski,Giuseppina Farina,Giuseppina Stifano,Allison L. Mathes,Marta Cossu,Michael York,Cindy Collins,Mark H. Wenink,R. Huijbens,Roger Hesselstrand,Tore Saxne,Michael DiMarzio,Dirk M. Wuttge,Sandeep K. Agarwal,John D. Reveille,Shervin Assassi,Maureen D. Mayes,Yanhui Deng,Joost P.H. Drenth,J. de Graaf,M. den Heijer,Cornelis Kallenberg,Marc Bijl,A. Loof,W.B. van den Berg,Leo A. B. Joosten,Vanessa Smith,F De Keyser,Raffaella Scorza,Claudio Lunardi,P.L.C.M. van Riel,Madelon C. Vonk,W.L. van Heerde,Stephan Meller,Bernhard Homey,Lorenzo Beretta,Mark Roest,Maria Trojanowska,Robert Lafyatis,Timothy R D J Radstake,Timothy R D J Radstake +48 more
TL;DR: Levels of CXCL4 were elevated in patients with systemic sclerosis and correlated with the presence and progression of complications, such as lung fibrosis and pulmonary arterial hypertension.
References
More filters
Journal ArticleDOI
PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses
Shaun Purcell,Shaun Purcell,Benjamin M. Neale,Benjamin M. Neale,Kathe Todd-Brown,Lori Thomas,Manuel A. R. Ferreira,David Bender,David Bender,Julian Maller,Julian Maller,Pamela Sklar,Pamela Sklar,Paul I.W. de Bakker,Paul I.W. de Bakker,Mark J. Daly,Mark J. Daly,Pak C. Sham +17 more
TL;DR: This work introduces PLINK, an open-source C/C++ WGAS tool set, and describes the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation, which focuses on the estimation and use of identity- by-state and identity/descent information in the context of population-based whole-genome studies.
Journal ArticleDOI
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
Paul Burton,David Clayton,Lon R. Cardon,Nicholas John Craddock,Panos Deloukas,Audrey Duncanson,Dominic P. Kwiatkowski,Mark I. McCarthy,Willem H. Ouwehand,Nilesh J. Samani,John A. Todd,Peter Donnelly,Jeffrey C. Barrett,Dan Davison,Doug Easton,David M. Evans,H. T. Leung,Jonathan Marchini,Andrew P. Morris,Chris C. A. Spencer,Martin D. Tobin,Antony P. Attwood,James P. Boorman,Barbara Cant,Ursula Everson,Judith M. Hussey,Jennifer Jolley,Alexandra S. Knight,Kerstin Koch,Elizabeth Meech,Sarah Nutland,Christopher Prowse,Helen Stevens,Niall C. Taylor,Graham R. Walters,Neil Walker,Nicholas A. Watkins,Thilo Winzer,Richard Jones,Wendy L. McArdle,Susan M. Ring,David P. Strachan,Marcus Pembrey,Gerome Breen,David St Clair,Sian Caesar,Katherine Gordon-Smith,Lisa Jones,Christine Fraser,Elaine K. Green,Detelina Grozeva,Marian L. Hamshere,Peter Holmans,Ian Jones,George Kirov,Valentina Moskvina,Ivan Nikolov,Michael Conlon O'Donovan,Michael John Owen,David A. Collier,Amanda Elkin,Anne Farmer,Richard Williamson,Peter McGuffin,Allan H. Young,I. Nicol Ferrier,Stephen G. Ball,Anthony J. Balmforth,Jennifer H. Barrett,D. Timothy Bishop,Mark M. Iles,Azhar Maqbool,Nadira Yuldasheva,Alistair S. Hall,Peter S. Braund,Richard J. Dixon,Massimo Mangino,Suzanne Stevens,John R. Thompson,Francesca Bredin,Mark Tremelling,Miles Parkes,Hazel E. Drummond,Charlie W. Lees,Elaine R. Nimmo,Jack Satsangi,Sheila A. Fisher,Alastair Forbes,Cathryn M. Lewis,Clive M. Onnie,Natalie J. Prescott,Jeremy D. Sanderson,Christopher G. Mathew,Jamie Barbour,M. Khalid Mohiuddin,Catherine E. Todhunter,John C. Mansfield,Tariq Ahmad,Fraser Cummings,Derek P. Jewell,John Webster,Morris J. Brown,G. Mark Lathrop,John M. C. Connell,Anna F. Dominiczak,Carolina A. Braga Marcano,Beverley Burke,Richard Dobson,Johannie Gungadoo,Kate L. Lee,Patricia B. Munroe,Stephen Newhouse,Abiodun Onipinla,Chris Wallace,Mingzhan Xue,Mark J. Caulfield,Martin Farrall,Anne Barton,Ian N. Bruce,Hannah Donovan,Steve Eyre,Paul D. Gilbert,Samantha L. Hider,Anne Hinks,Sally John,Catherine Potter,Alan J. Silman,Deborah P M Symmons,Wendy Thomson,Jane Worthington,David B. Dunger,Barry Widmer,Timothy M. Frayling,Rachel M. Freathy,Hana Lango,John R. B. Perry,Beverley M. Shields,Michael N. Weedon,Andrew T. Hattersley,Graham A. Hitman,Mark Walker,Kate S. Elliott,Christopher J. Groves,Cecilia M. Lindgren,Nigel W. Rayner,Nicholas J. Timpson,Eleftheria Zeggini,Melanie J. Newport,Giorgio Sirugo,Emily J. Lyons,Fredrik O. Vannberg,Adrian V. S. Hill,Linda A. Bradbury,C Farrar,J J Pointon,Paul Wordsworth,Matthew A. Brown,Jayne A. Franklyn,Joanne M. Heward,Matthew J. Simmonds,Stephen C. L. Gough,Sheila Seal,Michael R. Stratton,Nazneen Rahman,Maria Ban,An Goris,Stephen Sawcer,Alastair Compston,David J. Conway,Muminatou Jallow,Kirk A. Rockett,Suzannah Bumpstead,Amy Chaney,Kate Downes,Mohammed J. R. Ghori,Rhian Gwilliam,Sarah E. Hunt,Michael Inouye,Andrew Keniry,Emma King,Ralph McGinnis,Simon C. Potter,Rathi Ravindrarajah,Pamela Whittaker,Claire Widden,David Withers,Niall Cardin,Teresa Ferreira,Joanne Pereira-Gale,Ingileif B. Hallgrímsdóttir,Bryan Howie,Zhan Su,Yik Ying Teo,Damjan Vukcevic,David Bentley,A Compston +195 more
TL;DR: This study has demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in theBritish population is generally modest.
Journal ArticleDOI
Preliminary criteria for the classification of systemic sclerosis (scleroderma)
TL;DR: A multicenter, ongoing study of early-diagnosed cases of systemic sclerosis and comparison patients with systemic lupus erythematosus, polymyositis/dermatomyositis, and Raynaud's phenomenon was conducted in order to develop classification criteria for systemic sclerosis.
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Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee.
C Leroy,Roy D. Altman,J.B. Kirsner,Jonathan A. Myers,Dennis J. McShane,D. Masi,Gordon C. Sharp,Gerald P. Rodnan,A. MacKenzie-Graham,Thomas A. Medsger,James F. Fries +10 more
TL;DR: Proposed classification criteria for systemic sclerosis had a 97% sensitivity for definite systemic sclerosis and 98% specificity when applied to the case and comparison patients included in this study.
Journal ArticleDOI
Large recurrent microdeletions associated with schizophrenia
Hreinn Stefansson,Dan Rujescu,Sven Cichon,Olli Pietiläinen,Andres Ingason,Stacy Steinberg,Ragnheidur Fossdal,Engilbert Sigurdsson,Thordur Sigmundsson,Jacobine E. Buizer-Voskamp,Thomas Hansen,Thomas Hansen,Klaus D. Jakobsen,Klaus D. Jakobsen,Pierandrea Muglia,Clyde Francks,Paul M. Matthews,Arnaldur Gylfason,Bjarni V. Halldorsson,Daniel F. Gudbjartsson,Thorgeir E. Thorgeirsson,Asgeir Sigurdsson,Adalbjorg Jonasdottir,Aslaug Jonasdottir,Asgeir Björnsson,Sigurborg Mattiasdottir,Thorarinn Blondal,Magnús Haraldsson,Brynja B. Magnusdottir,Ina Giegling,Hans-Jürgen Möller,Annette M. Hartmann,Kevin V. Shianna,Dongliang Ge,Anna C. Need,Caroline Crombie,Gillian Fraser,Nicholas Walker,Jouko Lönnqvist,Jaana Suvisaari,Annamarie Tuulio-Henriksson,Tiina Paunio,T. Toulopoulou,Elvira Bramon,Marta Di Forti,Robin M. Murray,Mirella Ruggeri,Evangelos Vassos,Sarah Tosato,Muriel Walshe,Tao Li,Tao Li,Catalina Vasilescu,Thomas W. Mühleisen,August G. Wang,Henrik Ullum,Srdjan Djurovic,Ingrid Melle,Jes Olesen,Lambertus A. Kiemeney,Barbara Franke,Chiara Sabatti,Nelson B. Freimer,Jeffrey R. Gulcher,Unnur Thorsteinsdottir,Augustine Kong,Ole A. Andreassen,Roel A. Ophoff,Roel A. Ophoff,Alexander Georgi,Marcella Rietschel,Thomas Werge,Hannes Petursson,David Goldstein,Markus M. Nöthen,Leena Peltonen,Leena Peltonen,David A. Collier,David A. Collier,David St Clair,Kari Stefansson,Kari Stefansson +81 more
TL;DR: In a genome-wide search for CNVs associating with schizophrenia, a population-based sample was used to identify de novo CNVs by analysing 9,878 transmissions from parents to offspring and three deletions significantly associate with schizophrenia and related psychoses in the combined sample.
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