prior hypothesis based on gene function or disease pathways as described above. As a result, a number of novel targets with potential biological relevance have been discovered. For instance, GWA studies have found associations for genes involved in cell adhesion such as neurexin 1 (NRXN1) with nicotine dependence, while neurexin 3 (NRXN3) has been implicated with alcohol, opioid and polysubstance abuse (reviewed in (7), Supplementary Table 1). Furthermore, the association between the CHRNA5-A3-B4 gene cluster with smoking-related illnesses such as lung cancer and COPD was initially revealed by GWA studies that reported significant associations with the chromosomal regions 15q24-25 (reviewed in (12), Supplementary Table 1). These novel targets provide clues to the neurobiology of addiction, but require more detailed assessment of their functionality as discussed below.
