Given the wide range in severity of observed phenotypes in substance use and dependence, it is likely that genetic influences on substance problems are highly polygenic, that is, comprised of numerous small effects (e.g., Goldman et al., 2005). This is similar to other complex psychiatric and behavioral phenotypes (e.g., Plomin et al., 2009). A recent genome-wide study of schizophrenia identified a genetic score consisting of tens of thousands of SNPs that, in the aggregate, explained approximately 3% of the variance in schizophrenia case-control status (International Schizophrenia Consortium, 2009). While such genome-wide scores have the potential to explain significant variance, they do not necessarily provide greater information or discriminative ability than do established variants of known effect, in cases where such “known” variants exist (Evans et al., 2009). This may be in part due to the expected inclusion of “noise” variants (e.g., false-positive SNPs meeting selected significance cut-offs due to chance alone) when casting such a (genome)wide net as part of the scoring approach.
