Identification of gene-gene interaction using principal components

After more than 200 genome-wide association studies, there have been some successful identifications of a single novel locus. Thus, the identification of single-nucleotide polymorphisms (SNP) with interaction effects is of interest. Using the Genetic Analysis Workshop 16 data from the North American Rheumatoid Arthritis Consortium, we propose an approach to screen for SNP-SNP interaction using a two-stage method and an approach for detecting gene-gene interactions using principal components. We selected a set of 17 rheumatoid arthritis candidate genes to assess both approaches. Our approach using principal components holds promise in detecting gene-gene interactions. However, further study is needed to evaluate the power and the feasibility for a whole genome-wide association analysis using the principal components approach.