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
31 Citations (Scopus)


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.

Original languageEnglish
Article numberR6
JournalArthritis Research and Therapy
Issue number1
Publication statusPublished - 09.01.2014

Research Areas and Centers

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


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