title: Rheumatoid arthritis, item response theory, Blom transformation, and mixed models.
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.
authors.affiliation: Division of Statistical Genomics, Washington University School of Medicine, Division of Statistical Genomics, 4444 Forest Park Boulevard, Campus Box 8506, St, Louis, Missouri 63110, USA. aldi@wustl.edu
authors.forename: Aldi T
authors.initials: AT
authors.lastname: Kraja
authors.forename: Jon
authors.initials: J
authors.lastname: Corbett
authors.forename: An
authors.initials: A
authors.lastname: Ping
authors.forename: Rosa S
authors.initials: RS
authors.lastname: Lin
authors.forename: Petra A
authors.initials: PA
authors.lastname: Jacobsen
authors.forename: Michael
authors.initials: M
authors.lastname: Crosswhite
authors.forename: Ingrid B
authors.initials: IB
authors.lastname: Borecki
authors.forename: Michael A
authors.initials: MA
authors.lastname: Province