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

Lookup NU author(s): Professor Jaap van Laar

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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 x 10(-6), OR, 1.28) and CHRNA9 rs6832151 (P-MH = 4.30 x 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 x 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.


Publication metadata

Author(s): Lopez-Isac E, Bossini-Castillo L, Simeon CP, Egurbide MV, Alegre-Sancho JJ, Callejas JL, Roman-Ivorra JA, Freire M, Beretta L, Santaniello A, Airo 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, Spanish Scleroderma Grp

Publication type: Article

Publication status: Published

Journal: Arthritis Research and Therapy

Year: 2014

Volume: 16

Issue: 1

Pages: 1-8

Print publication date: 09/01/2014

Acceptance date: 18/12/2013

Date deposited: 27/08/2014

ISSN (print): 1478-6354

ISSN (electronic): 1478-6362

Publisher: BioMed Central Ltd.

URL: http://dx.doi.org/10.1186/ar4432

DOI: 10.1186/ar4432


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Funding

Funder referenceFunder name
KL2RR024149NCRR NIH HHS
K23AR061436NIAMS NIH HHS
R01-AR-055258NIAMS NIH HHS
P50 AR054144NIAMS NIH HHS
P50AR054144NIAMS NIH HHS
R01 AR055258NIAMS NIH HHS
U01 AI090909NIAID NIH HHS

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