Discussing gene-gene interaction: warning--translating equations to English may result in jabberwocky

Interest in mapping susceptibility alleles for complex diseases, which do not follow a classic single-gene segregation pattern, has driven interest in methods that account for, or use information from one locus when mapping another. Our discussion group examined methods related to epistasis or gene x gene interaction. The goal of modeling gene x gene interaction varied across groups; some papers tried to detect gene x gene interaction while others tried to exploit it to map genes. Most of the 10 papers summarized here applied newly created or newly modified statistical methods related to gene x gene interaction, while two groups primarily examined computational issues. As is often the case, comparisons are complicated by little overlap in the data used across the papers, and further complicated by the fact that the available data may not have been ideal for some gene x gene interaction methods. However, the main difficulty in comparing and contrasting methods across the papers is the lack of a consistent statistical definition of gene x gene interaction. But despite these issues, two clear trends emerged across the analyses: First, the methods for quantitative trait gene x gene interaction appeared to perform very well, even in families initially ascertained as affected sib pairs; and second, dichotomous trait gene x gene interaction methods failed to produce consistent results. The difficulty of using (primarily) affected sib pair data in a gene x gene interaction analysis is explored.