title: Investigation of rheumatoid arthritis genetic susceptibility markers in the early rheumatoid arthritis study further replicates the TRAF1 association with radiological damage.
abstract: OBJECTIVE
  The TRAF1 genetic region conferring susceptibility to rheumatoid arthritis (RA) has been reported to associate with radiological damage. We aimed to test RA genetic susceptibility markers for association with a continuous measure of radiological damage over time using longitudinal modeling techniques.
  
  
  METHODS
  Sixty-seven RA susceptibility variants were genotyped in 474 patients in the Early Rheumatoid Arthritis Study (ERAS) using Sequenom MassArray technology. Correlation between genetic markers and Larsen score was assessed longitudinally using zero-inflated negative binomial regression to include repeat measurements in the same individual at different timepoints. Genetic markers associated with radiological damage in ERAS were tested using the same modeling techniques on previously published data from the Norfolk Arthritis Register (NOAR).
  
  
  RESULTS
  The single marker associated longitudinally with Larsen score in ERAS (p = 0.02) and in NOAR (p = 0.04) was rs2900180 at the TRAF1 locus. Analysis of individual timepoints in ERAS showed that rs2900180 displays its effect primarily on the extent of Larsen score early in the disease course. Combined longitudinal analysis of the 2 cohorts suggests further association of several loci with Larsen score (KIF5A, PTPN22, AFF3, TAGAP) and therefore a significant accumulation of RA severity markers among RA susceptibility markers (p = 0.016).
  
  
  CONCLUSIONS
  The marker rs2900180 is associated with the extent of radiological damage in the ERAS cohort. This represents the second independent study correlating rs2900180 at the TRAF1 locus with radiological severity in RA. Replication in a large dataset is required to establish the role of other RA susceptibility loci in disease severity.
authors.affiliation: Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Viatte
authors.forename: Darren
authors.initials: D
authors.lastname: Plant
authors.forename: Mark
authors.initials: M
authors.lastname: Lunt
authors.forename: Bo
authors.initials: B
authors.lastname: Fu
authors.forename: Edward
authors.initials: E
authors.lastname: Flynn
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Parker
authors.forename: James
authors.initials: J
authors.lastname: Galloway
authors.forename: Csilla
authors.initials: C
authors.lastname: Solymossy
authors.forename: Jane
authors.initials: J
authors.lastname: Worthington
authors.forename: Deborah P M
authors.initials: DP
authors.lastname: Symmons
authors.forename: Josh J
authors.initials: JJ
authors.lastname: Dixey
authors.forename: Adam
authors.initials: A
authors.lastname: Young
authors.forename: Anne
authors.initials: A
authors.lastname: Barton
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000235:genetics*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011859:Radiography; D012042:Registries; D012044:Regression Analysis; D012720:Severity of Illness Index; D047990:TNF Receptor-Associated Factor 1 / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D047990:TNF Receptor-Associated Factor 1