A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci

Jose Ezequiel Martin; Shervin Assassi; Lina Marcela Diaz-Gallo; Jasper C. Broen; Carmen P. Simeon; Ivan Castellvi; Esther Vicente-Rabaneda; Vicente Fonollosa; Norberto Ortego-Centeno; Miguel A. González-Gay; Gerard Espinosa; Patricia Carreira; Mayte Camps; Jose M. Sabio; Sandra D'alfonso; Madelon C. Vonk; Alexandre E. Voskuyl; Annemie J. Schuerwegh; Alexander Kreuter; Torsten Witte; Gabriella Riemekasten; Nicolas Hunzelmann; Paolo Airo; Lorenzo Beretta; Raffaella Scorza; Claudio Lunardi; Jacob Van Laar; Meng May Chee; Jane Worthington; Arianne Herrick; Christopher Denton; Carmen Fonseca; Filemon K. Tan; Frank Arnett; Xiaodong Zhou; John D. Reveille; Olga Gorlova; Bobby P.C. Koeleman; Timothy R.D.J. Radstake; Timothy Vyse; Maureen D. Mayes; Marta E. Alarcón-Riquelme; Javier Martin

doi:10.1093/hmg/ddt248

A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci

Jose Ezequiel Martin^*, Shervin Assassi, Lina Marcela Diaz-Gallo, Jasper C. Broen, Carmen P. Simeon, Ivan Castellvi, Esther Vicente-Rabaneda, Vicente Fonollosa, Norberto Ortego-Centeno, Miguel A. González-Gay, Gerard Espinosa, Patricia Carreira, Mayte Camps, Jose M. Sabio, Sandra D'alfonso, Madelon C. Vonk, Alexandre E. Voskuyl, Annemie J. Schuerwegh, Alexander Kreuter, Torsten WitteGabriella Riemekasten, Nicolas Hunzelmann, Paolo Airo, Lorenzo Beretta, Raffaella Scorza, Claudio Lunardi, Jacob Van Laar, Meng May Chee, Jane Worthington, Arianne Herrick, Christopher Denton, Carmen Fonseca, Filemon K. Tan, Frank Arnett, Xiaodong Zhou, John D. Reveille, Olga Gorlova, Bobby P.C. Koeleman, Timothy R.D.J. Radstake, Timothy Vyse, Maureen D. Mayes, Marta E. Alarcón-Riquelme, Javier Martin

^*Corresponding author for this work

Clinic of Rheumatology

69 Citations (Scopus)

Abstract

Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are two archetypal systemic autoimmune diseases which have been shown to share multiple genetic susceptibility loci. In order to gain insight into the genetic basis of these diseases, we performed a pan-meta-analysis of two genome-wide association studies (GWASs) together with a replication stage including additional SSc and SLE cohorts. This increased the sample size to a total of 21 109 (6835 cases and 14 274 controls). We selected for replication 19 SNPs from the GWAS data. We were able to validate KIAA0319L (P = 3.31 × 10^-11, OR = 1.49) as novel susceptibility loci for SSc and SLE. Furthermore, we also determined that the previously described SLE susceptibility loci PXK (P = 3.27 × 10^-11, OR = 1.20) and JAZF1 (P = 1.11 × 10^-8, OR = 1.13) are shared with SSc. Supporting these new discoveries, we observed that KIAA0319L was overexpressed in peripheral blood cells of SSc and SLE patients compared with healthy controls. With these, we add three (KIAA0319L, PXK and JAZF1) and one (KIAA0319L) new susceptibility loci for SSc and SLE, respectively, increasing significantly the knowledge of the genetic basis of autoimmunity.

Original language	English
Journal	Human Molecular Genetics
Volume	22
Issue number	19
Pages (from-to)	4021-4029
Number of pages	9
ISSN	0964-6906
DOIs	https://doi.org/10.1093/hmg/ddt248
Publication status	Published - 10.2013

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

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10.1093/hmg/ddt248

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Martin, J. E., Assassi, S., Diaz-Gallo, L. M., Broen, J. C., Simeon, C. P., Castellvi, I., Vicente-Rabaneda, E., Fonollosa, V., Ortego-Centeno, N., González-Gay, M. A., Espinosa, G., Carreira, P., Camps, M., Sabio, J. M., D'alfonso, S., Vonk, M. C., Voskuyl, A. E., Schuerwegh, A. J., Kreuter, A., ... Martin, J. (2013). A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci. Human Molecular Genetics, 22(19), 4021-4029. https://doi.org/10.1093/hmg/ddt248

@article{e0d81ce6472c4e01b23ebbfcf475c548,

title = "A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci",

abstract = "Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are two archetypal systemic autoimmune diseases which have been shown to share multiple genetic susceptibility loci. In order to gain insight into the genetic basis of these diseases, we performed a pan-meta-analysis of two genome-wide association studies (GWASs) together with a replication stage including additional SSc and SLE cohorts. This increased the sample size to a total of 21 109 (6835 cases and 14 274 controls). We selected for replication 19 SNPs from the GWAS data. We were able to validate KIAA0319L (P = 3.31 × 10-11, OR = 1.49) as novel susceptibility loci for SSc and SLE. Furthermore, we also determined that the previously described SLE susceptibility loci PXK (P = 3.27 × 10-11, OR = 1.20) and JAZF1 (P = 1.11 × 10-8, OR = 1.13) are shared with SSc. Supporting these new discoveries, we observed that KIAA0319L was overexpressed in peripheral blood cells of SSc and SLE patients compared with healthy controls. With these, we add three (KIAA0319L, PXK and JAZF1) and one (KIAA0319L) new susceptibility loci for SSc and SLE, respectively, increasing significantly the knowledge of the genetic basis of autoimmunity.",

author = "Martin, {Jose Ezequiel} and Shervin Assassi and Diaz-Gallo, {Lina Marcela} and Broen, {Jasper C.} and Simeon, {Carmen P.} and Ivan Castellvi and Esther Vicente-Rabaneda and Vicente Fonollosa and Norberto Ortego-Centeno and Gonz{\'a}lez-Gay, {Miguel A.} and Gerard Espinosa and Patricia Carreira and Mayte Camps and Sabio, {Jose M.} and Sandra D'alfonso and Vonk, {Madelon C.} and Voskuyl, {Alexandre E.} and Schuerwegh, {Annemie J.} and Alexander Kreuter and Torsten Witte and Gabriella Riemekasten and Nicolas Hunzelmann and Paolo Airo and Lorenzo Beretta and Raffaella Scorza and Claudio Lunardi and {Van Laar}, Jacob and Chee, {Meng May} and Jane Worthington and Arianne Herrick and Christopher Denton and Carmen Fonseca and Tan, {Filemon K.} and Frank Arnett and Xiaodong Zhou and Reveille, {John D.} and Olga Gorlova and Koeleman, {Bobby P.C.} and Radstake, {Timothy R.D.J.} and Timothy Vyse and Mayes, {Maureen D.} and Alarc{\'o}n-Riquelme, {Marta E.} and Javier Martin",

note = "Funding Information: This work was supported by the following grants: J.M. was funded by GEN-FER from the Spanish Society of Rheumatology, SAF2009-11110 and SAF2012-34435 from the Ministerio de Economia y Competitividad, CTS-4977 from Junta de Andaluc{\'i}a (Spain), Redes Tem{\'a}ticas de Investigaci{\'o}n Coopera-tiva Sanitaria Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII, Spain), Fondo Europeo de Desarrollo Regional (FEDER) and the grant NIH NIAID 1U01AI09090-01. T.R.D.J.R. was funded by the VIDI laureate from the Dutch Association of Research (NWO) and Dutch Arthritis Foundation (National Reumafonds) and is an ERC starting grant Laureate 2011. J.M. and T.R.D.J.R. were sponsored by the Orphan Disease Program grant from the European League Against Rheumatism (EULAR). B.P.C.K. is supported by the Dutch Diabetes Research Foundation (grant 2008.40.001) and the Dutch Arthritis Foundation (Reumafonds, grant NR 09-1-408). S.A. and M.D.M. were supported by NIH/NIAMS Scleroderma Family Registry and DNA Repository (N01-AR-0-2251), NIH/NIAMS-RO1-AR055258, and NIH/ NIAMS Center of Research Translation in Scleroderma (1P50AR054144), the Department of Defense Congressionally Directed Medical Research Programs (W81XWH-07-01-0111), and K23-AR-061436. M.E.A.R. was funded by the Instituto de Salud Carlos III partially through FEDER funds of the European Union (PS09/00129), la Consejer{\'i}a de Salud de Andaluc{\'i}a (PI0012), la Fundaci{\'o}n Ram{\'o}n Areces and the Swedish Research Council. M.E.A.R. is the Chairman of the BIOLUPUS network funded by the European Science Foundation. T.W. is funded by the grant KFO 250, TP03, WI 1031/6-1. Copyright: Copyright 2014 Elsevier B.V., All rights reserved.",

year = "2013",

month = oct,

doi = "10.1093/hmg/ddt248",

language = "English",

volume = "22",

pages = "4021--4029",

journal = "Human Molecular Genetics",

issn = "0964-6906",

number = "19",

}

Martin, JE, Assassi, S, Diaz-Gallo, LM, Broen, JC, Simeon, CP, Castellvi, I, Vicente-Rabaneda, E, Fonollosa, V, Ortego-Centeno, N, González-Gay, MA, Espinosa, G, Carreira, P, Camps, M, Sabio, JM, D'alfonso, S, Vonk, MC, Voskuyl, AE, Schuerwegh, AJ, Kreuter, A, Witte, T, Riemekasten, G, Hunzelmann, N, Airo, P, Beretta, L, Scorza, R, Lunardi, C, Van Laar, J, Chee, MM, Worthington, J, Herrick, A, Denton, C, Fonseca, C, Tan, FK, Arnett, F, Zhou, X, Reveille, JD, Gorlova, O, Koeleman, BPC, Radstake, TRDJ, Vyse, T, Mayes, MD, Alarcón-Riquelme, ME & Martin, J 2013, 'A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci', Human Molecular Genetics, vol. 22, no. 19, pp. 4021-4029. https://doi.org/10.1093/hmg/ddt248

TY - JOUR

T1 - A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci

AU - Martin, Jose Ezequiel

AU - Assassi, Shervin

AU - Diaz-Gallo, Lina Marcela

AU - Broen, Jasper C.

AU - Simeon, Carmen P.

AU - Castellvi, Ivan

AU - Vicente-Rabaneda, Esther

AU - Fonollosa, Vicente

AU - Ortego-Centeno, Norberto

AU - González-Gay, Miguel A.

AU - Espinosa, Gerard

AU - Carreira, Patricia

AU - Camps, Mayte

AU - Sabio, Jose M.

AU - D'alfonso, Sandra

AU - Vonk, Madelon C.

AU - Voskuyl, Alexandre E.

AU - Schuerwegh, Annemie J.

AU - Kreuter, Alexander

AU - Witte, Torsten

AU - Riemekasten, Gabriella

AU - Hunzelmann, Nicolas

AU - Airo, Paolo

AU - Beretta, Lorenzo

AU - Scorza, Raffaella

AU - Lunardi, Claudio

AU - Van Laar, Jacob

AU - Chee, Meng May

AU - Worthington, Jane

AU - Herrick, Arianne

AU - Denton, Christopher

AU - Fonseca, Carmen

AU - Tan, Filemon K.

AU - Arnett, Frank

AU - Zhou, Xiaodong

AU - Reveille, John D.

AU - Gorlova, Olga

AU - Koeleman, Bobby P.C.

AU - Radstake, Timothy R.D.J.

AU - Vyse, Timothy

AU - Mayes, Maureen D.

AU - Alarcón-Riquelme, Marta E.

AU - Martin, Javier

N1 - Funding Information: This work was supported by the following grants: J.M. was funded by GEN-FER from the Spanish Society of Rheumatology, SAF2009-11110 and SAF2012-34435 from the Ministerio de Economia y Competitividad, CTS-4977 from Junta de Andalucía (Spain), Redes Temáticas de Investigación Coopera-tiva Sanitaria Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII, Spain), Fondo Europeo de Desarrollo Regional (FEDER) and the grant NIH NIAID 1U01AI09090-01. T.R.D.J.R. was funded by the VIDI laureate from the Dutch Association of Research (NWO) and Dutch Arthritis Foundation (National Reumafonds) and is an ERC starting grant Laureate 2011. J.M. and T.R.D.J.R. were sponsored by the Orphan Disease Program grant from the European League Against Rheumatism (EULAR). B.P.C.K. is supported by the Dutch Diabetes Research Foundation (grant 2008.40.001) and the Dutch Arthritis Foundation (Reumafonds, grant NR 09-1-408). S.A. and M.D.M. were supported by NIH/NIAMS Scleroderma Family Registry and DNA Repository (N01-AR-0-2251), NIH/NIAMS-RO1-AR055258, and NIH/ NIAMS Center of Research Translation in Scleroderma (1P50AR054144), the Department of Defense Congressionally Directed Medical Research Programs (W81XWH-07-01-0111), and K23-AR-061436. M.E.A.R. was funded by the Instituto de Salud Carlos III partially through FEDER funds of the European Union (PS09/00129), la Consejería de Salud de Andalucía (PI0012), la Fundación Ramón Areces and the Swedish Research Council. M.E.A.R. is the Chairman of the BIOLUPUS network funded by the European Science Foundation. T.W. is funded by the grant KFO 250, TP03, WI 1031/6-1. Copyright: Copyright 2014 Elsevier B.V., All rights reserved.

PY - 2013/10

Y1 - 2013/10

N2 - Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are two archetypal systemic autoimmune diseases which have been shown to share multiple genetic susceptibility loci. In order to gain insight into the genetic basis of these diseases, we performed a pan-meta-analysis of two genome-wide association studies (GWASs) together with a replication stage including additional SSc and SLE cohorts. This increased the sample size to a total of 21 109 (6835 cases and 14 274 controls). We selected for replication 19 SNPs from the GWAS data. We were able to validate KIAA0319L (P = 3.31 × 10-11, OR = 1.49) as novel susceptibility loci for SSc and SLE. Furthermore, we also determined that the previously described SLE susceptibility loci PXK (P = 3.27 × 10-11, OR = 1.20) and JAZF1 (P = 1.11 × 10-8, OR = 1.13) are shared with SSc. Supporting these new discoveries, we observed that KIAA0319L was overexpressed in peripheral blood cells of SSc and SLE patients compared with healthy controls. With these, we add three (KIAA0319L, PXK and JAZF1) and one (KIAA0319L) new susceptibility loci for SSc and SLE, respectively, increasing significantly the knowledge of the genetic basis of autoimmunity.

AB - Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are two archetypal systemic autoimmune diseases which have been shown to share multiple genetic susceptibility loci. In order to gain insight into the genetic basis of these diseases, we performed a pan-meta-analysis of two genome-wide association studies (GWASs) together with a replication stage including additional SSc and SLE cohorts. This increased the sample size to a total of 21 109 (6835 cases and 14 274 controls). We selected for replication 19 SNPs from the GWAS data. We were able to validate KIAA0319L (P = 3.31 × 10-11, OR = 1.49) as novel susceptibility loci for SSc and SLE. Furthermore, we also determined that the previously described SLE susceptibility loci PXK (P = 3.27 × 10-11, OR = 1.20) and JAZF1 (P = 1.11 × 10-8, OR = 1.13) are shared with SSc. Supporting these new discoveries, we observed that KIAA0319L was overexpressed in peripheral blood cells of SSc and SLE patients compared with healthy controls. With these, we add three (KIAA0319L, PXK and JAZF1) and one (KIAA0319L) new susceptibility loci for SSc and SLE, respectively, increasing significantly the knowledge of the genetic basis of autoimmunity.

UR - http://www.scopus.com/inward/record.url?scp=84888993757&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddt248

DO - 10.1093/hmg/ddt248

M3 - Journal articles

C2 - 23740937

AN - SCOPUS:84888993757

SN - 0964-6906

VL - 22

SP - 4021

EP - 4029

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 19

ER -

A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci

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