Complex phenotypes, including quantitative traits and common diseases, are controlled by many genes and by environmental factors. How do these genes combine to determine the phenotype of an individual? The simplest model is to assume that genes act additively with each other both within and between loci, but of course they may interact to show dominance or epistasis, respectively. A long standing controversy has existed concerning the importance of these non-additive effects, involving both Fisher [1] and Wright [2]. Estimates of genetic variance components within populations have indicated that most of the variance is additive [3],[4]. Increasing knowledge about biological pathways and gene networks implies, however, that gene-gene interactions (epistasis) are important, and some have argued recently that much genetic variance in populations is due to such interactions [5],[6],[7],[8]. It is important to distinguish between the observations of dominance or epistasis at the level of gene action at individual loci, exemplified by a table of genotypic values, and the observations of variance due to these components in analysis of data from a population. For example, at a completely dominant locus almost all the variance contributed is additive if the recessive gene is at high frequency [3],[4].
