Location of Repository

Rheumatoid arthritis, item response theory, Blom transformation, and mixed models

By Aldi T Kraja, Jon Corbett, An Ping, Rosa S Lin, Petra A Jacobsen, Michael Crosswhite, Ingrid B Borecki and Michael A Province

Abstract

We studied rheumatoid arthritis (RA) in the North American Rheumatoid Arthritis Consortium (NARAC) data (1499 subjects; 757 families). Identical methods were applied for studying RA in the Genetic Analysis Workshop 15 (GAW15) simulated data (with a prior knowledge of the simulation answers). Fifty replications of GAW15 simulated data had 3497 ± 20 subjects in 1500 nuclear families. Two new statistical methods were applied to transform the original phenotypes on these data, the item response theory (IRT) to create a latent variable from nine classifying predictors and a Blom transformation of the anti-CCP (anti-cyclic citrinullated protein) variable. We performed linear mixed-effects (LME) models to study the additive associations of 404 Illumina-genotyped single-nucleotide polymorphisms (SNPs) on the NARAC data, and of 17,820 SNPs of the GAW15 simulated data. In the GAW15 simulated data, the association with anti-CCP Blom transformation showed a 100% sensitivity for SNP1 located in the major histocompatibility complex gene. In contrast, the association of SNP1 with the IRT latent variable showed only 24% sensitivity. From the simulated data, we conclude that the Blom transformation of the anti-CCP variable produced more reliable results than the latent variable from the qualitative combination of a group of RA risk factors. In the NARAC data, the significant RA-SNPs associations found with both phenotype-transformation methods provided a trend that may point toward dynein and energy control genes. Finer genotyping in the NARAC data would grant more exact evidence for the contributions of chromosome 6 to RA

Topics: Proceedings
Publisher: BioMed Central
OAI identifier: oai:pubmedcentral.nih.gov:2367565
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles

    Preview

    Citations

    1. (2006). Anti-CCP antibodies measured at disease onset help identify seronegative rheumatoid arthritis and predict radiological and functional outcome. Rheumatology
    2. (2006). ltm: An R package for latent variable modeling and item response theory analyses.
    3. (2006). Moustaki I: Generalized latent variable models with non-linear effects. In
    4. (2000). PL: The prognostic value of anti-cyclic citrullinated peptide antibody in patients with recent-onset rheumatoid arthritis. Arthritis Rheum
    5. (1996). RD: SAS System for Mixed Models Cary, North Carolina:
    6. (2005). Refining the complex rheumatoid arthritis phenotype based on specificity of the HLA-DRB1 shared epitope for antibodies to citrullinated proteins. Arthritis Rheum
    7. (2001). Tozzoli R: Diagnostic accuracy of the anti-citrulline antibody assay for rheumatoid arthritis. Clin Chem
    8. (2000). Venrooij WJ: The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.