Genome-wide association study of response to tumour necrosis factor inhibitor therapy in rheumatoid arthritis.

ABSTRACT: Rheumatoid arthritis (RA) is characterised by chronic synovial joint inflammation. Treatment has been revolutionised by tumour necrosis factor alpha inhibitors (TNFi) but each available drug shows a significant non-response rate. We conducted a genome-wide association study of 1752 UK RA TNFi-treated patients to identify predictors of change in the Disease Activity Score 28 (DAS28) and subcomponents over 3-6 months. The rs7195994 variant at the FTO gene locus was associated with infliximab response when looking at a change in the swollen joint count (SJC28) subcomponent (p = 9.74 × 10^-9). Capture Hi-C data show chromatin interactions in GM12878 cells between rs2540767, in high linkage disequilibrium with rs7195994 (R² = 0.9) and IRX3, a neighbouring gene of FTO. IRX3

SUBMITTER: Massey J 

PROVIDER: S-EPMC6150911 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature