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.
Highlights
The data set of the North American Rheumatoid Arthritis Consortium (NARAC) for Genetic Analysis Workshop 15 (GAW15) contains genotypes of 5700 single-nucleotide polymorphism (SNP) covering all 23 human chromosomes, affected status of rheumatoid arthritis (RA), and a number of quantitative traits including anti-cyclic citrullinated peptide
The NARAC data set was edited by requiring each individual to have SNP genotypes on the 5700 SNPs and antiCCP record, and 1466 individuals satisfied this criterion
The three significant effects of two SNPs could be due to chance
Summary
The data set of the North American Rheumatoid Arthritis Consortium (NARAC) for Genetic Analysis Workshop 15 (GAW15) contains genotypes of 5700 SNPs covering all 23 human chromosomes, affected status of rheumatoid arthritis (RA), and a number of quantitative traits including anti-cyclic citrullinated peptide (anti-CCP). Anti-CCP is associated with RA and is used by some as a measure of RA [1]. Linkage analysis of the RA status in the NARAC data using affected sib-pair method has been reported [2]
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