Statistical analysis of genetic interactions.

Many common human diseases and complex traits are highly heritable and influenced by multiple genetic and environmental factors. Although genome-wide association studies (GWAS) have successfully identified many disease-associated variants, these genetic variants explain only a small proportion of the heritability of most complex diseases. Genetic interactions (gene-gene and gene-environment) substantially contribute to complex traits and diseases and could be one of the main sources of the missing heritability. This paper provides an overview of the available statistical methods and related computer software for identifying genetic interactions in animal and plant experimental crosses and human genetic association studies. The main discussion falls under the three broad issues in statistical analysis of genetic interactions: the definition, detection and interpretation of genetic interactions. Recently developed methods based on modern techniques for high-dimensional data are reviewed, including penalized likelihood approaches and hierarchical models; the relationships between these methods are also discussed. I conclude this review by highlighting some areas of future research.