Analysis of gene-gene interactions

Abstract

The goal of this unit is to introduce gene-gene interactions (epistasis) as a significant complicating factor in the search for disease susceptibility genes. This unit begins with an overview of gene-gene interactions and why they are likely to be common. Then, it reviews several statistical and computational methods for detecting and characterizing genes with effects that are dependent on other genes. The focus of this unit is genetic association studies of discrete and quantitative traits because most of the methods for detecting gene-gene interactions have been developed specifically for these study designs.

Figure 1.14.1

(A) Distribution of cases (diseased subjects; left bars) and controls (healthy subjects; right bars) across three genotypes (0, 1, 2) for two simulated interacting single nucleotide polymorphisms (SNPs). Note that the ratio of cases to controls for these two SNPs is nearly identical. The dark shaded cells signify “high-risk” genotypes (empirically determined). (B) Distribution of cases and controls across nine two-locus genotype combinations. Note that considering the two SNPs jointly reveals larger case-control ratios. Also illustrated is the use of the attribute construction function (see Ritchie et al., 2001 for MDR method) that produces a single attribute (SNP1_SNP2 with two levels, G₀ and G₁) from the two SNPs.