Several significant genetic associations have been detected in candidate gene and genome-wide association studies across several substances. In general, results confirm twin studies and indicate that SUD is polygenic; multiple genes of small effect contribute to SUD risk. Further, many of these genetic variants identified function within neurotransmitter pathways involved in the neurobiology of addicition (Drgon et al., 2010; Hardy & Singleton, 2009; Hirschhorn, 2009; Kraft & Hunter, 2009). Therefore, several genetic variants are expected to influence the neural substrates of addiction. However, genetic epidemiology studies of SUD must be evaluated in light of their limitations. Importantly, there remains an inconsistency in the replication of genetic association results. For example, although several significant genetic associations have been reported, few associations for nicotine dependence have replicated (Lerman & Berrettini, 2003; Quaak, van Schayck, Knaapen, & van Schooten, 2009). This may be due to a variety of reasons including: (1) low effect sizes of variants where each significant variant detected by a genetic association study will have a small influence on an SUD (Marjoram, Zubair, & Nuzhdin, 2014); (2) insufficient power to
