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Chunk #6 — Introduction

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Genetic influences on craving for alcohol.
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Based on this posited neurobiological basis of cue-elicited craving, we selected a set of genes that broadly constitute the dopamine system. These included receptor-encoding genes (DRD1, DRD2, DRD3, DRD4) and the dopamine (SLC6A3, also known as DAT) transporter gene. We also selected α-synuclein (SNCA) which was previously implicated in a candidate gene association study of alcohol craving conducted on a partially overlapping sample (Foroud et al., 2007) as well as in an independent sample (Bonsch et al., 2005b). While synucleins have been primarily studied in the context of Alzheimer’s and Parkinson’s disease (Irvine, El-Agnaf, Shankar, & Walsh, 2008), α-synucleins regulate dopamine D2 synthesis (Perez et al., 2002). Bonsch and colleagues found increased α-synuclein expression in alcoholics, which was positively correlated with alcohol craving scores (Bonsch et al., 2005a; Bonsch et al., 2004). In addition to this focus on dopamine pathway genes, in an effort to identify novel genetic variants that were associated with alcohol craving, we conducted a genomewide association study (GWAS).