This article is part of the supplement: Genetic Analysis Workshop 15: Gene Expression Analysis and Approaches to Detecting Multiple Functional Loci .

Proceedings

Genome-wide analysis of single-locus and epistasis single-nucleotide polymorphism effects on anti-cyclic citrullinated peptide as a measure of rheumatoid arthritis

Li Ma , Daniel Dvorkin , John R Garbe and Yang Da

Department of Animal Science, University of Minnesota, 1364 Eckles Avenue, St. Paul, Minnesota 55108, USA

author email corresponding author email

BMC Proceedings 2007, 1(Suppl 1):S127

Published:	18 December 2007

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 × additive, additive × dominance, dominance × additive, and dominance × 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.