A GWAS follow-up study reveals the association of the IL12RB2 gene with systemic sclerosis in Caucasian populations

摘要: A single-nucleotide polymorphism (SNP) at the IL12RB2 locus showed a suggestive association signal in previously published genome-wide study (GWAS) systemic sclerosis (SSc). Aiming to reveal possible implication of gene SSc, we conducted follow-up this different Caucasian cohorts. We analyzed 10 GWAS-genotyped SNPs region (2309 SSc patients and 5161 controls). then selected three (rs3790567, rs3790566 rs924080) based on their significance level GWAS, for an independent European cohort comprising 3344 3848 controls. The most-associated SNP (rs3790567) was further tested 597 1139 controls from USA. After conditional logistic regression analysis GWAS data, rs3790567 [P-MH = 1.92 x 10(-5) odds ratio (OR) 1.19] as genetic variant with firmest observed peak association. first phase, only consistent (P-MH 4.84 10(-3) OR 1.12). second phase confirmed finding (P-chi 2 2.82 10(-4) 1.34). performing overall pooled-analysis all cohorts included present study, found reached GWAS-level significant 10(-9) 1.17). Our data clearly support suggest relevant role interleukin 12 signaling pathway pathogenesis.