Genetic associations with radiological damage in rheumatoid arthritis: Meta-analysis of seven genome-wide association studies of 2,775 cases

Matthew Traylor, Rachel Knevel, Jing Cui, John Taylor, Westra Harm-Jan, Philip G Conaghan, Andrew P Cope, Charles Curtis, Paul Emery, Stephen Newhouse, Hamel Patel, Sophia Steer, Peter Gregersen, Nancy A Shadick, Michael E Weinblatt, Annette Van Der Helm-van Mil, Jennifer H Barrett, Ann W Morgan, Cathryn M Lewis and Ian C Scott

PLOS ONE, 2019, vol. 14, issue 10, 1-12

Abstract: Background: Previous studies of radiological damage in rheumatoid arthritis (RA) have used candidate-gene approaches, or evaluated single genome-wide association studies (GWAS). We undertook the first meta-analysis of GWAS of RA radiological damage to: (1) identify novel genetic loci for this trait; and (2) test previously validated variants. Methods: Seven GWAS (2,775 RA cases, of a range of ancestries) were combined in a meta-analysis. Radiological damage was assessed using modified Larsen scores, Sharp van Der Heijde scores, and erosive status. Single nucleotide polymophsim (SNP) associations with radiological damage were tested at a single time-point using regression models. Primary analyses included age and disease duration as covariates. Secondary analyses also included rheumatoid factor (RF). Meta-analyses were undertaken in trans-ethnic and European-only cases. Results: In the trans-ethnic primary meta-analysis, one SNP (rs112112734) in close proximity to HLA-DRB1, and strong linkage disequilibrium with the shared-epitope, attained genome-wide significance (P = 4.2x10-8). In the secondary analysis (adjusting for RF) the association was less significant (P = 1.7x10-6). In both trans-ethnic primary and secondary meta-analyses 14 regions contained SNPs with associations reaching P

Date: 2019
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0223246

DOI: 10.1371/journal.pone.0223246

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