research and/or theoretical literature exists to allow for the a priori selection of a pathway for inclusion in the construction of a targeted scoring approach. The current findings demonstrate that such a candidate system scoring approach may be potentially useful to the investigation of genetic effects on complex phenotypes. In such situations it is likely that numerous genetic variants within a system of biologically plausible genes each exert a relatively small effect, and the influence of these genes may only be reliably detected when they are considered in the aggregate. Therefore, we suggest that using strict criteria for individual candidate SNP replication across samples may discard SNPs that, if their effects were considered in aggregate, may have a significant impact on the phenotype of interest.
