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Thursday, May 31, 2007

CNR1 Variation Modulates Risk for Drug and Alcohol Dependence
Biological Psychiatry
Article in Press, On-line 23 May 2007

Human cannabinoid receptor 1 (CB1), which is encoded by the CNR1 gene, may play a role in the development of substance dependence (SD). Following initial reports of association of CNR1 with SD, we studied multiple markers at this locus in a large case–control sample.

In EAs, risk for each SD subtype significantly increased with the number of “G” alleles at rs6454674 (single nucleotide polymorphisms [SNP]3). SNP3^G+ (the genotypes containing a G allele) and SNP8^T/T genotypes had significant interaction effects (p = .0003 for comorbid DD and AD, .0002 for DD, and .007 for AD). SNP3 and SNP8 together exerted stronger genetic effects on SD than either did individually. The peak δ values among all the markers were seen for SNP3 and SNP8 (rs806368).

We demonstrate that CNR1 variation and interactive effects play important roles in risk for both DD and AD.

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Reprint Request E-mail: joel.gelernter@yale.edu

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