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• W2771000689 abstract "Objective Rheumatoid arthritis ( RA ) is a genetically complex disease of immune dysregulation. This study sought to gain further insight into the genetic risk mechanisms of RA by conducting an expression quantitative trait locus ( eQTL ) analysis of confirmed genetic risk loci in CD 4+ T cells and B cells from carefully phenotyped patients with early arthritis who were naive to therapeutic immunomodulation. Methods RNA and DNA were isolated from purified B and/or CD 4+ T cells obtained from the peripheral blood of 344 patients with early arthritis. Genotyping and global gene expression measurements were carried out using Illumina BeadChip microarrays. Variants in linkage disequilibrium ( LD ) with non‐ HLA RA single‐nucleotide polymorphisms (defined as r 2 ≥ 0.8) were analyzed, seeking evidence of cis ‐ or trans ‐ eQTL s according to whether the associated probes were or were not within 4 Mb of these LD blocks. Results Genes subject to cis ‐ eQTL effects that were common to both CD 4+ and B lymphocytes at RA risk loci were FADS 1 , FADS 2 , BLK , FCRL 3 , ORMDL 3 , PPIL 3 , and GSDMB . In contrast, those acting on METTL 21B , JAZF 1 , IKZF 3, and PADI 4 were unique to CD 4+ lymphocytes, with the latter candidate risk gene being identified for the first time in this cell subset. B lymphocyte–specific eQTL s for SYNGR 1 and CD 83 were also found. At the 8p23 BLK – FAM 167A locus, adjacent genes were subject to eQTL s whose activity differed markedly between cell types; in particular, the FAM 167A effect displayed striking B lymphocyte specificity. No trans ‐ eQTL s approached experiment‐wide significance, and linear modeling did not identify a significant influence of biologic covariates on cis ‐ eQTL effect sizes. Conclusion These findings further refine the understanding of candidate causal genes in RA pathogenesis, thus providing an important platform from which downstream functional studies, directed toward particular cell types, may be prioritized." @default.
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• W2771000689 date "2018-01-30" @default.
• W2771000689 modified "2023-10-16" @default.
• W2771000689 title "CD4+ and B Lymphocyte Expression Quantitative Traits at Rheumatoid Arthritis Risk Loci in Patients With Untreated Early Arthritis" @default.
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• W2771000689 doi "https://doi.org/10.1002/art.40393" @default.
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