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

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Evaluating gene × gene and gene × smoking interaction in rheumatoid arthritis using candidate genes in GAW15

Ling Mei*, Xiaohui Li, Kai Yang, Jinrui Cui, Belle Fang, Xiuqing Guo and Jerome I Rotter

Author Affiliations

Department of Medical Genetics, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, 665 West Tower, Los Angeles, California 90048, USA

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BMC Proceedings 2007, 1(Suppl 1):S17  doi:

Published: 18 December 2007


We examined the potential gene × gene interactions and gene × smoking interactions in rheumatoid arthritis (RA) using the candidate gene data sets provided by Genetic Analysis Workshop 15 Problem 2. The multifactor dimensionality reduction (MDR) method was used to test gene × gene interactions among candidate genes. The case-only sample was used to test gene × smoking interactions. The best predictive model was the single-locus model with single-nucleotide polymorphism (SNP) rs2476601 in gene PTPN22. However, no clear gene × gene interaction was identified. Substantial departure from multiplicativity was observed between smoking and SNPs in genes CTLA4, PADI4, MIF, and SNPs on chromosome 5 and one haplotype of PTPN22. The strongest evidence of association was identified between the PTPN22 gene and RA status, which was consistently detected in single SNP association, gene × gene interaction and gene × smoking interaction analyses.