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Chunk #2 — Introduction

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SNPs in CHRNA6 and CHRNB3 are associated with alcohol consumption in a nationally representative sample.
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However, only four studies have looked directly for an association between human polymorphisms in nAChRs and alcohol behaviors (Ehringer et al., 2007; Schlaepfer et al., 2008a; Wang et al., 2008; Zeiger et al., 2008). Evidence for alcohol-related behaviors was found in three of these (Ehringer et al., 2007; Schlaepfer et al., 2008a; Wang et al., 2008), but not in the only study which examined the CHRNB3/A6 genes (Zeiger et al., 2008). Among the few genome wide association studies conducted on alcoholism in adult samples, genes for the nAChRs have not emerged as top candidates (Johnson et al., 2006; Zhu et al., 2005). Among the receptor types expressed on dopaminergic nerve terminals, only the α6 and β3 subunits show localized expression to dopamine neurons, whereas α4 and β2 are expressed throughout the brain and α5 is primarily expressed in the periphery (Putz et al., 2008). Furthermore, α6 and β3 are likely to be co-regulated since they are adjacently located in the genome and co-localized to the substantia nigra, ventral tegmental area, striatum, and locus coeruleus (Gotti et al., 2006). However, in