Gene-Gene and Gene-Environment Interactions Underlying Complex Traits and their Detection.

Among these methods emerged recently, data reduction approaches (a constructive induction strategy) such as the multifactor dimensionality reduction method (MDR) [36,37], the combinatorial partitioning method [38], and the restricted partition method [39], are promising to address the multidimensionality problems. Rather than modeling the interaction term per se as with regression methods, a data reduction strategy seeks for a pattern in a combination of factors/ attributes of interest that maximizes the phenotypic variation it explains. It treats the joint action as a whole, coinciding to the very original epitasis coined by Bateson [40], offering a solution that avoids decomposition as in regression methods where the number of interaction parameters grows exponentially as each new variable is added. It also has a straightforward correspondence to the concept of the phenotypic landscape that unifies biological, statistical genetics and evolutionary theories [41-45]. Notably the pioneering MDR method has sustained its popularity in detection of interactions since its launch [46].