A Refined Study of FCRL Genes from a Genome-Wide Association Study for Graves’ Disease

摘要: To pinpoint the exact location of etiological variant/s present at 1q21.1 harboring FCRL1-5 and CD5L genes, we carried out a refined association study in entire FCRL region 1,536 patients with Graves’ disease (GD) 1,516 sex-matched controls by imputation analysis, logistic regression, cis-eQTL analysis. Among 516 SNPs P<0.05 initial GWAS scan, strongest signals associated GD correlated to FCRL3 expression were located cluster including rs7528684 rs3761959. And allele-specific effects for rs3761959 on level revealed that risk alleles A C elevated whether PBMCs or its subsets, especially CD19+ B cells CD8+ T subsets. Next, combined analysis 5,300 cases 4,916 control individuals confirmed was susceptibility gene Chinese Han populations, met genome-wide significance (Pcombined = 2.27×10−12 7.11×10−13, respectively). Moreover, haplotypes allele risk. Finally, our epigenetic suggested disease-associated increased affinity NF-KB transcription factor. Above data indicated proxy SNP may be involved pathogenesis excessive inhibiting cell receptor signaling impairment suppressing function Tregs.