Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus

Timothy R D J Radstake; Olga Gorlova; Blanca Rueda; Jose Ezequiel Martin; Behrooz Z. Alizadeh; Rogelio Palomino-Morales; Marieke J. Coenen; Madelon C. Vonk; Alexandre E. Voskuyl; Annemie J. Schuerwegh; Jasper C. Broen; Piet L C M Van Riel; Ruben Van 'T Slot; Annet Italiaander; Roel A. Ophoff; Gabriela Riemekasten; Nico Hunzelmann; Carmen P. Simeon; Norberto Ortego-Centeno; Miguel A. González-Gay; María F. González-Escribano; Paolo Airo; Jaap Van Laar; Ariane Herrick; Jane Worthington; Roger Hesselstrand; Vanessa Smith; Filip De Keyser; Fredric Houssiau; Meng May Chee; Rajan Madhok; Paul Shiels; Rene Westhovens; Alexander Kreuter; Hans 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 T. Lee; Jun Ying; Younghun Han; Shih Feng Weng; Christopher I. Amos; Fredrick M. Wigley; Laura Hummers; J. Lee Nelson; Sandeep K. Agarwal; Shervin Assassi; Pravitt Gourh; Filemon K. Tan; Bobby P C Koeleman; Frank C. Arnett; Javier Martin; Maureen D. Mayes

doi:10.1038/ng.565

Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus

Timothy R D J Radstake, Olga Gorlova, Blanca Rueda, Jose Ezequiel Martin, Behrooz Z. Alizadeh, Rogelio Palomino-Morales, Marieke J. Coenen, Madelon C. Vonk, Alexandre E. Voskuyl, Annemie J. Schuerwegh, Jasper C. Broen, Piet L C M Van Riel, Ruben Van 'T Slot, Annet Italiaander, Roel A. Ophoff, Gabriela Riemekasten, Nico Hunzelmann, Carmen P. Simeon, Norberto Ortego-Centeno, Miguel A. González-GayMaría F. González-Escribano, Paolo Airo, Jaap Van Laar, Ariane Herrick, Jane Worthington, Roger Hesselstrand, Vanessa Smith, Filip De Keyser, Fredric Houssiau, Meng May Chee, Rajan Madhok, Paul Shiels, Rene Westhovens, Alexander Kreuter, Hans 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 T. Lee, Jun Ying, Younghun Han, Shih Feng Weng, Christopher I. Amos, Fredrick M. Wigley, Laura Hummers, J. Lee Nelson, Sandeep K. Agarwal, Shervin Assassi, Pravitt Gourh, Filemon K. Tan, Bobby P C Koeleman, Frank C. Arnett, Javier Martin, Maureen D. Mayes

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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 × 10 7 in the discovery samples, P = 3.39 × 10 9 in the combined analysis). Additionally, we confirm and firmly establish the role of the MHC (P = 2.31 × 10 18), IRF5 (P = 1.86 × 10 13) and STAT4 (P = 3.37 × 10 9) gene regions as SSc genetic risk factors. © 2010 Nature America, Inc. All rights reserved.

Original language	English
Pages (from-to)	426-429
Number of pages	3
Journal	Nature Genetics
Volume	42
Issue number	5
DOIs	https://doi.org/10.1038/ng.565
Publication status	Published - May 2010

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Radstake, T. R. D. J., Gorlova, O., Rueda, B., Martin, J. E., Alizadeh, B. Z., Palomino-Morales, R., Coenen, M. J., Vonk, M. C., Voskuyl, A. E., Schuerwegh, A. J., Broen, J. C., Van Riel, P. L. C. M., Van 'T Slot, R., Italiaander, A., Ophoff, R. A., Riemekasten, G., Hunzelmann, N., Simeon, C. P., Ortego-Centeno, N., ... Mayes, M. D. (2010). Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus. Nature Genetics, 42(5), 426-429. https://doi.org/10.1038/ng.565

@article{519357e49f3a4b3ba37f838d31eb36d7,

title = "Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus",

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 × 10 7 in the discovery samples, P = 3.39 × 10 9 in the combined analysis). Additionally, we confirm and firmly establish the role of the MHC (P = 2.31 × 10 18), IRF5 (P = 1.86 × 10 13) and STAT4 (P = 3.37 × 10 9) gene regions as SSc genetic risk factors. {\textcopyright} 2010 Nature America, Inc. All rights reserved.",

author = "Radstake, {Timothy R D J} and Olga Gorlova and Blanca Rueda and Martin, {Jose Ezequiel} and Alizadeh, {Behrooz Z.} and Rogelio Palomino-Morales and Coenen, {Marieke J.} and Vonk, {Madelon C.} and Voskuyl, {Alexandre E.} and Schuerwegh, {Annemie J.} and Broen, {Jasper C.} and {Van Riel}, {Piet L C M} and {Van 'T Slot}, Ruben and Annet Italiaander and Ophoff, {Roel A.} and Gabriela Riemekasten and Nico Hunzelmann and Simeon, {Carmen P.} and Norberto Ortego-Centeno and Gonz{\'a}lez-Gay, {Miguel A.} and Gonz{\'a}lez-Escribano, {Mar{\'i}a F.} and Paolo Airo and {Van Laar}, Jaap and Ariane Herrick and Jane Worthington and Roger Hesselstrand and Vanessa Smith and {De Keyser}, Filip and Fredric Houssiau and Chee, {Meng May} and Rajan Madhok and Paul Shiels and Rene Westhovens and Alexander Kreuter and Hans Kiener and {De Baere}, Elfride and Torsten Witte and Leonid Padykov and Lars Klareskog and Lorenzo Beretta and Rafaella Scorza and Lie, {Benedicte A.} and Hoffmann-Vold, {Anna Maria} and Patricia Carreira and John Varga and Monique Hinchcliff and Gregersen, {Peter K.} and Lee, {Annette T.} and Jun Ying and Younghun Han and Weng, {Shih Feng} and Amos, {Christopher I.} and Wigley, {Fredrick M.} and Laura Hummers and Nelson, {J. Lee} and Agarwal, {Sandeep K.} and Shervin Assassi and Pravitt Gourh and Tan, {Filemon K.} and Koeleman, {Bobby P C} and Arnett, {Frank C.} and Javier Martin and Mayes, {Maureen D.}",

note = "17552, Arthritis Research Campaign, United Kingdom3UL1RR024148, NCRR NIH HHS, United StatesK08 AR054404-02, NIAMS NIH HHS, United StatesK08AR054404, NIAMS NIH HHS, United StatesN01 AR002251-013, NIAMS NIH HHS, United StatesN01-AR-02251, NIAMS NIH HHS, United StatesP50 AR054144-04, NIAMS NIH HHS, United StatesP50AR054144, NIAMS NIH HHS, United StatesR01 AI041721-12, NIAID NIH HHS, United StatesR01 AR055258, NIAMS NIH HHS, United StatesR01 AR055258-02, NIAMS NIH HHS, United StatesR01 MH078075, NIMH NIH HHS, United StatesR01 MH078075-04, NIMH NIH HHS, United StatesUL1 RR024148-02, NCRR NIH HHS, United States",

year = "2010",

month = may,

doi = "10.1038/ng.565",

language = "English",

volume = "42",

pages = "426--429",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "5",

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Radstake, TRDJ, Gorlova, O, Rueda, B, Martin, JE, Alizadeh, BZ, Palomino-Morales, R, Coenen, MJ, Vonk, MC, Voskuyl, AE, Schuerwegh, AJ, Broen, JC, Van Riel, PLCM, Van 'T Slot, R, Italiaander, A, Ophoff, RA, Riemekasten, G, Hunzelmann, N, Simeon, CP, Ortego-Centeno, N, González-Gay, MA, González-Escribano, MF, Airo, P, Van Laar, J, Herrick, A , Worthington, J, Hesselstrand, R, Smith, V, De Keyser, F, Houssiau, F, Chee, MM, Madhok, R, Shiels, P, Westhovens, R, Kreuter, A, Kiener, H, De Baere, E, Witte, T, Padykov, L, Klareskog, L, Beretta, L, Scorza, R, Lie, BA, Hoffmann-Vold, AM, Carreira, P, Varga, J, Hinchcliff, M, Gregersen, PK, Lee, AT, Ying, J, Han, Y, Weng, SF, Amos, CI, Wigley, FM, Hummers, L, Nelson, JL, Agarwal, SK, Assassi, S, Gourh, P, Tan, FK, Koeleman, BPC, Arnett, FC, Martin, J & Mayes, MD 2010, 'Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus', Nature Genetics, vol. 42, no. 5, pp. 426-429. https://doi.org/10.1038/ng.565

TY - JOUR

T1 - Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus

AU - Radstake, Timothy R D J

AU - Gorlova, Olga

AU - Rueda, Blanca

AU - Martin, Jose Ezequiel

AU - Alizadeh, Behrooz Z.

AU - Palomino-Morales, Rogelio

AU - Coenen, Marieke J.

AU - Vonk, Madelon C.

AU - Voskuyl, Alexandre E.

AU - Schuerwegh, Annemie J.

AU - Broen, Jasper C.

AU - Van Riel, Piet L C M

AU - Van 'T Slot, Ruben

AU - Italiaander, Annet

AU - Ophoff, Roel A.

AU - Riemekasten, Gabriela

AU - Hunzelmann, Nico

AU - Simeon, Carmen P.

AU - Ortego-Centeno, Norberto

AU - González-Gay, Miguel A.

AU - González-Escribano, María F.

AU - Airo, Paolo

AU - Van Laar, Jaap

AU - Herrick, Ariane

AU - Worthington, Jane

AU - Hesselstrand, Roger

AU - Smith, Vanessa

AU - De Keyser, Filip

AU - Houssiau, Fredric

AU - Chee, Meng May

AU - Madhok, Rajan

AU - Shiels, Paul

AU - Westhovens, Rene

AU - Kreuter, Alexander

AU - Kiener, Hans

AU - De Baere, Elfride

AU - Witte, Torsten

AU - Padykov, Leonid

AU - Klareskog, Lars

AU - Beretta, Lorenzo

AU - Scorza, Rafaella

AU - Lie, Benedicte A.

AU - Hoffmann-Vold, Anna Maria

AU - Carreira, Patricia

AU - Varga, John

AU - Hinchcliff, Monique

AU - Gregersen, Peter K.

AU - Lee, Annette T.

AU - Ying, Jun

AU - Han, Younghun

AU - Weng, Shih Feng

AU - Amos, Christopher I.

AU - Wigley, Fredrick M.

AU - Hummers, Laura

AU - Nelson, J. Lee

AU - Agarwal, Sandeep K.

AU - Assassi, Shervin

AU - Gourh, Pravitt

AU - Tan, Filemon K.

AU - Koeleman, Bobby P C

AU - Arnett, Frank C.

AU - Martin, Javier

AU - Mayes, Maureen D.

N1 - 17552, Arthritis Research Campaign, United Kingdom3UL1RR024148, NCRR NIH HHS, United StatesK08 AR054404-02, NIAMS NIH HHS, United StatesK08AR054404, NIAMS NIH HHS, United StatesN01 AR002251-013, NIAMS NIH HHS, United StatesN01-AR-02251, NIAMS NIH HHS, United StatesP50 AR054144-04, NIAMS NIH HHS, United StatesP50AR054144, NIAMS NIH HHS, United StatesR01 AI041721-12, NIAID NIH HHS, United StatesR01 AR055258, NIAMS NIH HHS, United StatesR01 AR055258-02, NIAMS NIH HHS, United StatesR01 MH078075, NIMH NIH HHS, United StatesR01 MH078075-04, NIMH NIH HHS, United StatesUL1 RR024148-02, NCRR NIH HHS, United States

PY - 2010/5

Y1 - 2010/5

N2 - 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 × 10 7 in the discovery samples, P = 3.39 × 10 9 in the combined analysis). Additionally, we confirm and firmly establish the role of the MHC (P = 2.31 × 10 18), IRF5 (P = 1.86 × 10 13) and STAT4 (P = 3.37 × 10 9) gene regions as SSc genetic risk factors. © 2010 Nature America, Inc. All rights reserved.

AB - 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 × 10 7 in the discovery samples, P = 3.39 × 10 9 in the combined analysis). Additionally, we confirm and firmly establish the role of the MHC (P = 2.31 × 10 18), IRF5 (P = 1.86 × 10 13) and STAT4 (P = 3.37 × 10 9) gene regions as SSc genetic risk factors. © 2010 Nature America, Inc. All rights reserved.

U2 - 10.1038/ng.565

DO - 10.1038/ng.565

M3 - Article

C2 - 20383147

SN - 1061-4036

VL - 42

SP - 426

EP - 429

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus

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