Background: 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. Methods: Ten CNR1 markers and 38 ancestry-informative markers were genotyped in 451 healthy control subjects and 550 SD (AD and/or DD) patients (including European Americans [EAs] and African Americans [AAs]). Common confounding effects on association analysis of population stratification and admixture, age, and sex were controlled for using regression analysis. Disease risk and protective alleles were fine-mapped using a linkage disequilibrium measure (δ). Results: 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). Conclusions: We demonstrate that CNR1 variation and interactive effects play important roles in risk for both DD and AD. © 2007 Society of Biological Psychiatry.
CITATION STYLE
Zuo, L., Kranzler, H. R., Luo, X., Covault, J., & Gelernter, J. (2007). CNR1 Variation Modulates Risk for Drug and Alcohol Dependence. Biological Psychiatry, 62(6), 616–626. https://doi.org/10.1016/j.biopsych.2006.12.004
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