A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility

Elena López-Isac; Lara Bossini-Castillo; Carmen Pilar Simeón; María V. Egurbide; Juan J. Alegre-Sancho; Jose L. Callejas; José A. Roman-Ivorra; Mayka Freire; Lorenzo Beretta; Alessandro Santaniello; Paolo Airó; Claudio Lunardi; Nicolas Hunzelmann; Gabriela Riemekasten; Torsten Witte; Alexander Kreuter; Jörg H.W. Distler; Annemie J. Schuerwegh; Madelon C. Vonk; Alexandre E. Voskuyl; Paul G. Shiels; Jacob M. van Laar; Carmen Fonseca; Christopher Denton; Ariane Herrick; Jane Worthington; Shervin Assassi; Bobby P. Koeleman; Maureen D. Mayes; Timothy R.D.J. Radstake; Javier Martin; Norberto Ortego-Centeno; Raquel Ríos; Nuria Navarrete; Rosa García Portales; María Teresa Camps; Antonio Fernández-Nebro; María F. González-Escribano; Julio Sánchez-Román; Francisco José García-Hernández; Ma Jesús Castillo; Ma Ángeles Aguirre; Inmaculada Gómez-Gracia; Patricia Carreira; Benjamín Fernández-Gutiérrez; Luis Rodríguez-Rodríguez; Esther Vicente; José Luis Andreu; Mónica Fernández de Castro; Paloma García de la Peña; Francisco Javier López-Longo; Lina Martinez; Vicente Fonollosa; Carmen Pilar Simeón; Gerard Espinosa; Ivá Castellví; Carlos Tolosa; Anna Pros; Mónica Rodríguez Carballeira; Francisco Javier Narváez; Manel Rubio Rivas; Vera Ortiz Santamarí; Miguel Ángel González-Gay; Bernardino Díaz; Luis Trapiella; Adrián Sousa; Patricia Fanlo Mateo; Luis Sáez-Comet; Federico Díaz; Vanesa Hernández; Emma Beltrán; Francisco J. Blanco García; Natividad Oreiro

doi:10.1186/ar4432

A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility

Elena López-Isac, Lara Bossini-Castillo, Carmen Pilar Simeón, María V. Egurbide, Juan J. Alegre-Sancho, Jose L. Callejas, José A. Roman-Ivorra, Mayka Freire, Lorenzo Beretta, Alessandro Santaniello, Paolo Airó, Claudio Lunardi, Nicolas Hunzelmann, Gabriela Riemekasten, Torsten Witte, Alexander Kreuter, Jörg H.W. Distler, Annemie J. Schuerwegh, Madelon C. Vonk, Alexandre E. VoskuylPaul G. Shiels, Jacob M. van Laar, Carmen Fonseca, Christopher Denton, Ariane Herrick, Jane Worthington, Shervin Assassi, Bobby P. Koeleman, Maureen D. Mayes, Timothy R.D.J. Radstake, Javier Martin^*, Norberto Ortego-Centeno, Raquel Ríos, Nuria Navarrete, Rosa García Portales, María Teresa Camps, Antonio Fernández-Nebro, María F. González-Escribano, Julio Sánchez-Román, Francisco José García-Hernández, Ma Jesús Castillo, Ma Ángeles Aguirre, Inmaculada Gómez-Gracia, Patricia Carreira, Benjamín Fernández-Gutiérrez, Luis Rodríguez-Rodríguez, Esther Vicente, José Luis Andreu, Mónica Fernández de Castro, Paloma García de la Peña, Francisco Javier López-Longo, Lina Martinez, Vicente Fonollosa, Carmen Pilar Simeón, Gerard Espinosa, Ivá Castellví, Carlos Tolosa, Anna Pros, Mónica Rodríguez Carballeira, Francisco Javier Narváez, Manel Rubio Rivas, Vera Ortiz Santamarí, Miguel Ángel González-Gay, Bernardino Díaz, Luis Trapiella, Adrián Sousa, Patricia Fanlo Mateo, Luis Sáez-Comet, Federico Díaz, Vanesa Hernández, Emma Beltrán, Francisco J. Blanco García, Natividad Oreiro

^*Corresponding author for this work

Clinic of Rheumatology

31 Citations (Scopus)

Abstract

Introduction: A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy.Methods: Sixty-six non-HLA SNPs showing a P value <10^-4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed by using TaqMan SNP genotyping assays.Results: We observed nominal associations for both PPARG rs310746 (P_MH = 1.90 × 10^-6, OR, 1.28) and CHRNA9 rs6832151 (P_MH = 4.30 × 10^-6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value = 0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (P_MH = 5.00 × 10^-7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis.Conclusion: Our results suggest a role of PPARG gene in the development of SSc.

Original language	English
Article number	R6
Journal	Arthritis Research and Therapy
Volume	16
Issue number	1
ISSN	1478-6354
DOIs	https://doi.org/10.1186/ar4432
Publication status	Published - 09.01.2014

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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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10.1186/ar4432

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López-Isac, E., Bossini-Castillo, L., Simeón, C. P., Egurbide, M. V., Alegre-Sancho, J. J., Callejas, J. L., Roman-Ivorra, J. A., Freire, M., Beretta, L., Santaniello, A., Airó, P., Lunardi, C., Hunzelmann, N., Riemekasten, G., Witte, T., Kreuter, A., Distler, J. H. W., Schuerwegh, A. J., Vonk, M. C., ... Oreiro, N. (2014). A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility. Arthritis Research and Therapy, 16(1), Article R6. https://doi.org/10.1186/ar4432

@article{336dc5685d79467c9444a9d5d68c1fb6,

title = "A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility",

abstract = "Introduction: A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy.Methods: Sixty-six non-HLA SNPs showing a P value <10-4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed by using TaqMan SNP genotyping assays.Results: We observed nominal associations for both PPARG rs310746 (PMH = 1.90 × 10-6, OR, 1.28) and CHRNA9 rs6832151 (PMH = 4.30 × 10-6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value = 0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (PMH = 5.00 × 10-7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis.Conclusion: Our results suggest a role of PPARG gene in the development of SSc.",

author = "Elena L{\'o}pez-Isac and Lara Bossini-Castillo and Sime{\'o}n, {Carmen Pilar} and Egurbide, {Mar{\'i}a V.} and Alegre-Sancho, {Juan J.} and Callejas, {Jose L.} and Roman-Ivorra, {Jos{\'e} A.} and Mayka Freire and Lorenzo Beretta and Alessandro Santaniello and Paolo Air{\'o} and Claudio Lunardi and Nicolas Hunzelmann and Gabriela Riemekasten and Torsten Witte and Alexander Kreuter and Distler, {J{\"o}rg H.W.} and Schuerwegh, {Annemie J.} and Vonk, {Madelon C.} and Voskuyl, {Alexandre E.} and Shiels, {Paul G.} and {van Laar}, {Jacob M.} and Carmen Fonseca and Christopher Denton and Ariane Herrick and Jane Worthington and Shervin Assassi and Koeleman, {Bobby P.} and Mayes, {Maureen D.} and Radstake, {Timothy R.D.J.} and Javier Martin and Norberto Ortego-Centeno and Raquel R{\'i}os and Nuria Navarrete and Portales, {Rosa Garc{\'i}a} and Camps, {Mar{\'i}a Teresa} and Antonio Fern{\'a}ndez-Nebro and Gonz{\'a}lez-Escribano, {Mar{\'i}a F.} and Julio S{\'a}nchez-Rom{\'a}n and Garc{\'i}a-Hern{\'a}ndez, {Francisco Jos{\'e}} and Castillo, {Ma Jes{\'u}s} and Aguirre, {Ma {\'A}ngeles} and Inmaculada G{\'o}mez-Gracia and Patricia Carreira and Benjam{\'i}n Fern{\'a}ndez-Guti{\'e}rrez and Luis Rodr{\'i}guez-Rodr{\'i}guez and Esther Vicente and Andreu, {Jos{\'e} Luis} and {de Castro}, {M{\'o}nica Fern{\'a}ndez} and {de la Pe{\~n}a}, {Paloma Garc{\'i}a} and L{\'o}pez-Longo, {Francisco Javier} and Lina Martinez and Vicente Fonollosa and Sime{\'o}n, {Carmen Pilar} and Gerard Espinosa and Iv{\'a} Castellv{\'i} and Carlos Tolosa and Anna Pros and Carballeira, {M{\'o}nica Rodr{\'i}guez} and Narv{\'a}ez, {Francisco Javier} and Rivas, {Manel Rubio} and Santamar{\'i}, {Vera Ortiz} and Gonz{\'a}lez-Gay, {Miguel {\'A}ngel} and Bernardino D{\'i}az and Luis Trapiella and Adri{\'a}n Sousa and Mateo, {Patricia Fanlo} and Luis S{\'a}ez-Comet and Federico D{\'i}az and Vanesa Hern{\'a}ndez and Emma Beltr{\'a}n and {Blanco Garc{\'i}a}, {Francisco J.} and Natividad Oreiro",

year = "2014",

month = jan,

day = "9",

doi = "10.1186/ar4432",

language = "English",

volume = "16",

journal = "Arthritis Research and Therapy",

issn = "1478-6354",

number = "1",

}

López-Isac, E, Bossini-Castillo, L, Simeón, CP, Egurbide, MV, Alegre-Sancho, JJ, Callejas, JL, Roman-Ivorra, JA, Freire, M, Beretta, L, Santaniello, A, Airó, P, Lunardi, C, Hunzelmann, N, Riemekasten, G, Witte, T, Kreuter, A, Distler, JHW, Schuerwegh, AJ, Vonk, MC, Voskuyl, AE, Shiels, PG, van Laar, JM, Fonseca, C, Denton, C, Herrick, A, Worthington, J, Assassi, S, Koeleman, BP, Mayes, MD, Radstake, TRDJ, Martin, J, Ortego-Centeno, N, Ríos, R, Navarrete, N, Portales, RG, Camps, MT, Fernández-Nebro, A, González-Escribano, MF, Sánchez-Román, J, García-Hernández, FJ, Castillo, MJ, Aguirre, MÁ, Gómez-Gracia, I, Carreira, P, Fernández-Gutiérrez, B, Rodríguez-Rodríguez, L, Vicente, E, Andreu, JL, de Castro, MF, de la Peña, PG, López-Longo, FJ, Martinez, L, Fonollosa, V, Simeón, CP, Espinosa, G, Castellví, I, Tolosa, C, Pros, A, Carballeira, MR, Narváez, FJ, Rivas, MR, Santamarí, VO, González-Gay, MÁ, Díaz, B, Trapiella, L, Sousa, A, Mateo, PF, Sáez-Comet, L, Díaz, F, Hernández, V, Beltrán, E, Blanco García, FJ & Oreiro, N 2014, 'A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility', Arthritis Research and Therapy, vol. 16, no. 1, R6. https://doi.org/10.1186/ar4432

TY - JOUR

T1 - A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility

AU - López-Isac, Elena

AU - Bossini-Castillo, Lara

AU - Simeón, Carmen Pilar

AU - Egurbide, María V.

AU - Alegre-Sancho, Juan J.

AU - Callejas, Jose L.

AU - Roman-Ivorra, José A.

AU - Freire, Mayka

AU - Beretta, Lorenzo

AU - Santaniello, Alessandro

AU - Airó, Paolo

AU - Lunardi, Claudio

AU - Hunzelmann, Nicolas

AU - Riemekasten, Gabriela

AU - Witte, Torsten

AU - Kreuter, Alexander

AU - Distler, Jörg H.W.

AU - Schuerwegh, Annemie J.

AU - Vonk, Madelon C.

AU - Voskuyl, Alexandre E.

AU - Shiels, Paul G.

AU - van Laar, Jacob M.

AU - Fonseca, Carmen

AU - Denton, Christopher

AU - Herrick, Ariane

AU - Worthington, Jane

AU - Assassi, Shervin

AU - Koeleman, Bobby P.

AU - Mayes, Maureen D.

AU - Radstake, Timothy R.D.J.

AU - Martin, Javier

AU - Ortego-Centeno, Norberto

AU - Ríos, Raquel

AU - Navarrete, Nuria

AU - Portales, Rosa García

AU - Camps, María Teresa

AU - Fernández-Nebro, Antonio

AU - González-Escribano, María F.

AU - Sánchez-Román, Julio

AU - García-Hernández, Francisco José

AU - Castillo, Ma Jesús

AU - Aguirre, Ma Ángeles

AU - Gómez-Gracia, Inmaculada

AU - Carreira, Patricia

AU - Fernández-Gutiérrez, Benjamín

AU - Rodríguez-Rodríguez, Luis

AU - Vicente, Esther

AU - Andreu, José Luis

AU - de Castro, Mónica Fernández

AU - de la Peña, Paloma García

AU - López-Longo, Francisco Javier

AU - Martinez, Lina

AU - Fonollosa, Vicente

AU - Simeón, Carmen Pilar

AU - Espinosa, Gerard

AU - Castellví, Ivá

AU - Tolosa, Carlos

AU - Pros, Anna

AU - Carballeira, Mónica Rodríguez

AU - Narváez, Francisco Javier

AU - Rivas, Manel Rubio

AU - Santamarí, Vera Ortiz

AU - González-Gay, Miguel Ángel

AU - Díaz, Bernardino

AU - Trapiella, Luis

AU - Sousa, Adrián

AU - Mateo, Patricia Fanlo

AU - Sáez-Comet, Luis

AU - Díaz, Federico

AU - Hernández, Vanesa

AU - Beltrán, Emma

AU - Blanco García, Francisco J.

AU - Oreiro, Natividad

PY - 2014/1/9

Y1 - 2014/1/9

N2 - Introduction: A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy.Methods: Sixty-six non-HLA SNPs showing a P value <10-4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed by using TaqMan SNP genotyping assays.Results: We observed nominal associations for both PPARG rs310746 (PMH = 1.90 × 10-6, OR, 1.28) and CHRNA9 rs6832151 (PMH = 4.30 × 10-6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value = 0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (PMH = 5.00 × 10-7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis.Conclusion: Our results suggest a role of PPARG gene in the development of SSc.

AB - Introduction: A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy.Methods: Sixty-six non-HLA SNPs showing a P value <10-4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed by using TaqMan SNP genotyping assays.Results: We observed nominal associations for both PPARG rs310746 (PMH = 1.90 × 10-6, OR, 1.28) and CHRNA9 rs6832151 (PMH = 4.30 × 10-6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value = 0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (PMH = 5.00 × 10-7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis.Conclusion: Our results suggest a role of PPARG gene in the development of SSc.

UR - http://www.scopus.com/inward/record.url?scp=84892166010&partnerID=8YFLogxK

U2 - 10.1186/ar4432

DO - 10.1186/ar4432

M3 - Journal articles

C2 - 24401602

AN - SCOPUS:84892166010

SN - 1478-6354

VL - 16

JO - Arthritis Research and Therapy

JF - Arthritis Research and Therapy

IS - 1

M1 - R6

ER -

A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility

Abstract

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