RT Journal Article
SR Electronic
T1 Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 1548
OP 1553
DO 10.1136/ard.2009.121020
VO 69
IS 8
A1 Darren Plant
A1 Edward Flynn
A1 Hamdi Mbarek
A1 Philippe Dieudé
A1 François Cornelis
A1 Lisbeth Ärlestig
A1 Solbritt Rantapää Dahlqvist
A1 George Goulielmos
A1 Dimitrios T Boumpas
A1 Prodromos Sidiropoulos
A1 Julia S Johansen
A1 Lykke M Ørnbjerg
A1 Merete Lund Hetland
A1 Lars Klareskog
A1 Andrew Filer
A1 Christopher D Buckley
A1 Karim Raza
A1 Torsten Witte
A1 Reinhold E Schmidt
A1 Jane Worthington
YR 2010
UL http://ard.bmj.com/content/69/8/1548.abstract
AB Background Genetic factors have a substantial role in determining development of rheumatoid arthritis (RA), and are likely to account for 50–60% of disease susceptibility. Genome-wide association studies have identified non-human leucocyte antigen RA susceptibility loci which associate with RA with low-to-moderate risk. Objectives To investigate recently identified RA susceptibility markers using cohorts from six European countries, and perform a meta-analysis including previously published results. Methods 3311 DNA samples were collected from patients from six countries (UK, Germany, France, Greece, Sweden and Denmark). Genotype data or DNA samples for 3709 controls were collected from four countries (not Sweden or Denmark). Eighteen single nucleotide polymorphisms (SNPs) were genotyped using Sequenom MassArray technology. Samples with a >95% success rate and only those SNPs with a genotype success rate of >95% were included in the analysis. Scandinavian patient data were pooled and previously published Swedish control data were accessed as a comparison group. Meta-analysis was used to combine results from this study with all previously published data. Results After quality control, 3209 patients and 3692 controls were included in the study. Eight markers (ie, rs1160542 (AFF3), rs1678542 (KIF5A), rs2476601 (PTPN22), rs3087243 (CTLA4), rs4810485 (CD40), rs5029937 (6q23), rs10760130 (TRAF1/C5) and rs7574865 (STAT4)) were significantly associated with RA by meta-analysis. All 18 markers were associated with RA when previously published studies were incorporated in the analysis. Data from this study increased the significance for association with RA and nine markers. Conclusions In a large European RA cohort further evidence for the association of 18 markers with RA development has been obtained.