Variants in GABRA2 are strongly associated with alcoholism,24–27 but an association has been reported between GABRA2 variants and addiction to nicotine and polysubstance abuse.56,57 Furthermore, a linkage study has implicated the region near GABRA2 in the etiology of cannabis use.58 Variants in ANKK1, a protein kinase involved in signal transduction,59 have also been associated with susceptibility to ND,60,61 AD, 62,63 and comorbid alcohol and drug dependence.64 Finally, several GWASs provide evidence for the involvement of cell adhesion-related genes in vulnerability to addiction and other psychiatric disorders.65 Representative members of this category include neurexin 1 for ND66,67 and neurexin 3 for polysubstance,65 alcohol,68 and opioid abuse.69 Rare mutations in several members of this gene family, including neurexin 1, also have been associated with autism54,70 and schizophrenia,71 implying the members of this family are important in many psychiatric disorders.
