title: A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  Our results suggest a role of PPARG gene in the development of SSc.
authors.forename: Elena
authors.initials: E
authors.lastname: López-Isac
authors.forename: Lara
authors.initials: L
authors.lastname: Bossini-Castillo
authors.forename: Carmen P
authors.initials: CP
authors.lastname: Simeon
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Egurbide
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Alegre-Sancho
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Callejas
authors.forename: José Andrés
authors.initials: JA
authors.lastname: Roman-Ivorra
authors.forename: Mayka
authors.initials: M
authors.lastname: Freire
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Beretta
authors.forename: Alessandro
authors.initials: A
authors.lastname: Santaniello
authors.forename: Paolo
authors.initials: P
authors.lastname: Airó
authors.forename: Claudio
authors.initials: C
authors.lastname: Lunardi
authors.forename: Nicolas
authors.initials: N
authors.lastname: Hunzelmann
authors.forename: Gabriela
authors.initials: G
authors.lastname: Riemekasten
authors.forename: Torsten
authors.initials: T
authors.lastname: Witte
authors.forename: Alexander
authors.initials: A
authors.lastname: Kreuter
authors.forename: Jörg H W
authors.initials: JH
authors.lastname: Distler
authors.forename: Annemie J
authors.initials: AJ
authors.lastname: Schuerwegh
authors.forename: Madelon C
authors.initials: MC
authors.lastname: Vonk
authors.forename: Alexandre E
authors.initials: AE
authors.lastname: Voskuyl
authors.forename: Paul G
authors.initials: PG
authors.lastname: Shiels
authors.forename: Jacob M
authors.initials: JM
authors.lastname: van Laar
authors.forename: Carmen
authors.initials: C
authors.lastname: Fonseca
authors.forename: Christopher
authors.initials: C
authors.lastname: Denton
authors.forename: Ariane
authors.initials: A
authors.lastname: Herrick
authors.forename: Jane
authors.initials: J
authors.lastname: Worthington
authors.forename: Shervin
authors.initials: S
authors.lastname: Assassi
authors.forename: Bobby P
authors.initials: BP
authors.lastname: Koeleman
authors.forename: Maureen D
authors.initials: MD
authors.lastname: Mayes
authors.forename: Timothy R D J
authors.initials: TR
authors.lastname: Radstake
authors.forename: Javier
authors.initials: J
authors.lastname: Martin
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012595:Scleroderma, Systemic / Q000235:genetics*
chemical_list: D047495:PPAR gamma