title: Genome-wide analysis of single-locus and epistasis single-nucleotide polymorphism effects on anti-cyclic citrullinated peptide as a measure of rheumatoid arthritis.
abstract: The goal of this study was to identify single-locus and epistasis effects of SNP markers on anti-cyclic citrullinated peptide (anti-CCP) that is associated with rheumatoid arthritis, using the North American Rheumatoid Arthritis Consortium data. A square root transformation of the phenotypic values of anti-CCP with sex, smoking status, and a selected subset of 20 single-nucleotide polymorphism (SNP) markers in the model achieved residual normality (p > 0.05). Three single-locus effects of two SNPs were significant (p < 10-4). The epistasis analysis tested five effects of each pair of SNPs, the two-locus interaction, additive x additive, additive x dominance, dominance x additive, and dominance x dominance effects. A total of ten epistasis effects of eight pairs of SNPs on 11 autosomes and the X chromosome had significant epistasis effects (p < 10-7). Three of these epistasis effects reached significance levels of p < 10-8, p < 10-9, and p < 10-10, respectively. Two potential SNP epistasis networks were identified. The results indicate that the genetic factors underlying anti-CCP may include single-gene action and gene interactions and that the gene-interaction mechanism underlying anti-CCP could be a complex mechanism involving pairwise epistasis effects and multiple SNPs.
authors.affiliation: Department of Animal Science, University of Minnesota, 1364 Eckles Avenue, St, Paul, Minnesota 55108, USA. maxxx131@umn.edu
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Daniel
authors.initials: D
authors.lastname: Dvorkin
authors.forename: John R
authors.initials: JR
authors.lastname: Garbe
authors.forename: Yang
authors.initials: Y
authors.lastname: Da