Whole genome approaches address the vexed question of the genetic architecture of psychiatric disease: that is to say, how many loci are involved, how common are the variants, and what is the distribution of their effect sizes? A very practical concern drives this seemingly arcane question, namely, will it be possible to find genes in which mutations are the main, if not the sole, predisposing genetic cause? Finding even one such gene would provide a starting point for investigating disease pathogenesis because it is now relatively straightforward to model highly penetrant alleles, whereas it is not clear how to model a small effect locus that acts as part of a polygenic system to exert its effect on a phenotype.
