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

Clinic of Rheumatology

284 Citations (Scopus)

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.

Original language	English
Journal	Nature Genetics
Volume	42
Issue number	5
Pages (from-to)	426-429
Number of pages	4
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.565
Publication status	Published - 05.2010

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Academic Focus: Center for Infection and Inflammation Research (ZIEL)

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ng.565

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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{4cbfd186f6994be4be768ab1e2b1910c,

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.",

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 = "Funding Information: This work was supported by the following grants: T.R.D.J.R. was funded by the VIDI laureate from the Dutch Association of Research (NWO) and Dutch Arthritis Foundation (National Reumafonds). J.M. was funded by GEN-FER from the Spanish Society of Rheumatology, SAF2009-11110 from the Spanish Ministry of Science, CTS-4977 from Junta de Andaluc{\'i}a, Spain and in part by Redes Tem{\'a}ticas de Investigaci{\'o}n Cooperativa Sanitaria Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), Spain (J.M.). R.B. is supported by the I3P Consejo Superior de Investigaciones Cient{\'i}ficas program funded by the {\textquoteleft}Fondo Social Europeo{\textquoteright}. B.Z.A. is supported by the Netherlands Organization for Health Research and Development (ZonMW grant 016.096.121). B.K. is supported by the Dutch Diabetes Research Foundation (grant 2008.40.001) and the Dutch Arthritis Foundation (Reumafonds, grant NR 09-1-408). Genotyping of the Dutch control samples was sponsored by US National Insitutes of Mental Health funding, R01 MH078075 (R.O.A.). The German controls were from the PopGen biobank (to B.K.). The PopGen project received infrastructure support through the German Research Foundation excellence cluster {\textquoteleft}Inflammation at Interfaces{\textquoteright}. The US analyses were supported by the US National Institutes of Health and National Institute of Arthritis and Musculoskeletal Diseases (NIH-NIAMS) R01 AR055258, Two-Stage Genome Wide Association Study in Systemic Sclerosis, (M.D.M.) and by the NIH-NIAMS Center of Research Translation (CORT) in SSc (P50AR054144) (F.C.A.), the NIH-NIAMS SSc Family Registry and DNA Repository (N01-AR-0-2251) (M.D.M.), University of Texas Health Science Center-Houston Center for Clinical and Translational Sciences (Houston Clinical and Translational Science Awards Program) (NIH-National Center for Research Resources 3UL1RR024148) (F.C.A.), NIH-NIAMS K08 Award (K08AR054404) (S.K.A.), SSc Foundation New Investigator Award (S.K.A.). Copyright: Copyright 2010 Elsevier B.V., All rights reserved.",

year = "2010",

month = may,

doi = "10.1038/ng.565",

language = "English",

volume = "42",

pages = "426--429",

journal = "Nature Genetics",

issn = "1061-4036",

number = "5",

}

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 - Funding Information: This work was supported by the following grants: T.R.D.J.R. was funded by the VIDI laureate from the Dutch Association of Research (NWO) and Dutch Arthritis Foundation (National Reumafonds). J.M. was funded by GEN-FER from the Spanish Society of Rheumatology, SAF2009-11110 from the Spanish Ministry of Science, CTS-4977 from Junta de Andalucía, Spain and in part by Redes Temáticas de Investigación Cooperativa Sanitaria Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), Spain (J.M.). R.B. is supported by the I3P Consejo Superior de Investigaciones Científicas program funded by the ‘Fondo Social Europeo’. B.Z.A. is supported by the Netherlands Organization for Health Research and Development (ZonMW grant 016.096.121). B.K. is supported by the Dutch Diabetes Research Foundation (grant 2008.40.001) and the Dutch Arthritis Foundation (Reumafonds, grant NR 09-1-408). Genotyping of the Dutch control samples was sponsored by US National Insitutes of Mental Health funding, R01 MH078075 (R.O.A.). The German controls were from the PopGen biobank (to B.K.). The PopGen project received infrastructure support through the German Research Foundation excellence cluster ‘Inflammation at Interfaces’. The US analyses were supported by the US National Institutes of Health and National Institute of Arthritis and Musculoskeletal Diseases (NIH-NIAMS) R01 AR055258, Two-Stage Genome Wide Association Study in Systemic Sclerosis, (M.D.M.) and by the NIH-NIAMS Center of Research Translation (CORT) in SSc (P50AR054144) (F.C.A.), the NIH-NIAMS SSc Family Registry and DNA Repository (N01-AR-0-2251) (M.D.M.), University of Texas Health Science Center-Houston Center for Clinical and Translational Sciences (Houston Clinical and Translational Science Awards Program) (NIH-National Center for Research Resources 3UL1RR024148) (F.C.A.), NIH-NIAMS K08 Award (K08AR054404) (S.K.A.), SSc Foundation New Investigator Award (S.K.A.). Copyright: Copyright 2010 Elsevier B.V., All rights reserved.

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.

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.

UR - http://www.scopus.com/inward/record.url?scp=77951765348&partnerID=8YFLogxK

U2 - 10.1038/ng.565

DO - 10.1038/ng.565

M3 - Journal articles

C2 - 20383147

AN - SCOPUS:77951765348

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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