%0 Journal Article
%T Gene-gene and gene-environment interactions: new insights into the prevention, detection and management of coronary artery disease
%A Matthew B Lanktree
%A Robert A Hegele
%J Genome Medicine
%D 2009
%I BioMed Central
%R 10.1186/gm28
%X Genetic investigations of coronary artery disease (CAD) aim to identify functional variants to assist with its diagnosis, prognosis or treatment. The full spectrum of DNA variant sizes and frequencies, ranging from single nucleotide changes to large copy number variations and from rare mutations to common polymorphisms, are components of a comprehensive approach to identify genetic determinants of CAD. However, CAD is the terminal manifestation of multiple intermediate disease processes, which individually have genetic and environmental determinants (Figure 1). For genetic research into CAD to be truly comprehensive, experimental methods must identify environmental and genetic factors and their interactions [1,2].It seems reasonable that the effect of a CAD susceptibility allele could differ depending on the context of other genetic or environmental factors. For instance, is it effective to search for a gene underlying type 2 diabetes mellitus (T2DM) in high performance athletes? Although such athletes may be genetically predisposed to T2DM, their activity levels would probably protect them from expressing the phenotype. However, although gene-gene or gene-environment interactions seem to be an obvious topic for consideration, the analysis of such interactions is not yet routine in genetic studies of CAD. Here, we will focus on interaction types, strategies to detect interactions, potential biases and the statistical issues involved in studying gene-gene and gene-environment interactions in CAD.Broadly defined, interactions are differences in the strength of association between a gene and phenotype on the basis of the presence of, absence of or quantitative differences in an additional factor, which could be another genetic variant or an environmental exposure. There are several putative models for gene-environment interactions, including synergy, modification of effects and redundancy (Figure 2). For a gene-gene interaction, the additional factor might be dichotomo
%U http://genomemedicine.com/content/1/2/28