Alcohol and nicotine co-dependence may represent a more severe subtype of alcohol dependence. A large number of risk loci have been associated with both alcohol dependence and nicotine dependence by candidate gene approach, including many genes that are involved in the dopaminergic, serotoninergic, GABAergic, glutamatergic, cholinergic, opioid and endocannabinoid systems. However, none of these genes have been confirmed by recent genome-wide association studies (GWASs) of alcohol dependence (Treutlein et al., 2009; Bierut et al., 2010; Edenberg et al., 2010; Heath et al., 2011; Johnson et al., 2011). Only two of them (CHRNA6-CHRNB3 (Thorgeirsson et al., 2010) and CHRNA5-CHRNA3-CHRNB4 (Liu et al., 2010)) were confirmed by meta-analysis GWASs of nicotine dependence. GWASs of alcohol dependence or alcohol consumption reported multiple other potential risk loci (Treutlein et al., 2009; Bierut et al., 2010; Edenberg et al., 2010; Heath et al., 2011; Schumann et al., 2011), so did most GWASs of nicotine dependence. To date, there has been only one GWAS (Lind et al., 2010) directly studying the phenotype of alcohol and nicotine co-dependence. That study identified three risk genes including ARHGAP10, MARK1 and DDX6. However, those findings have not been replicated independently yet.
