ABSTRACT
The search for susceptibility loci in the study of common, complex diseases is a major challenge in the field of human genetics, and has been less successful than for simple Mendelian disorders (Moore, 2003). It is likely that this is due to many complicating factors such as an increased number of contributing loci and susceptibility alleles, incomplete penetrance, and contributing environmental effects (Templeton, 2000; Cordell, 2002; Culverhouse et al., 2002; Moore and Williams, 2002; Moore, 2003; Sing et al., 2004; Thornton-Wells et al., 2004). Additionally, gene-gene and gene-environment interaction, or epistasis, is an increasingly assumed to play an important role in the underlying etiology of such diseases (Templeton, 2000; Cordell, 2002; Culverhouse et al., 2002; Moore and Williams, 2002; Moore, 2003; Sing et al., 2004; Thornton-Wells et al., 2004). While there are several definitions of the word “epistasis”, in its simplest definition, epistasis occurs when the action of one gene is modified by one or more other genetic and/or environmental factors. This phenomenon presents a challenge in the search for disease-risk variants, since if the effect of one locus is altered or masked by effects at another locus, the power to detect the first locus is likely to be reduced and elucidation of the joint effects at the two loci will be hindered by their interaction, unless explicitly examined (Cordell, 2002).
