Agrawal Arpana, Wetherill Leah, Dick Danielle M, Xuei Xiaoling, Hinrichs Anthony, Hesselbrock Victor, Kramer John, Nurnberger John I, Schuckit Marc, Bierut Laura J, Edenberg Howard J, Foroud Tatiana
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Am J Med Genet B Neuropsychiatr Genet. 2009 Jul 5;150B(5):736-40. doi: 10.1002/ajmg.b.30881.
Genomic studies of cannabis use disorders have been limited. The cannabinoid receptor 1 gene (CNR1) on chromosome 6q14-15 is an excellent candidate gene for cannabis dependence due to the important role of the G-protein coupled receptor encoded by this gene in the rewarding effects of Delta9-tetrahydrocannabinol. Previous studies have found equivocal evidence for an association between SNPs in CNR1 and a general vulnerability to substance use disorders. We investigate the association between 9 SNPs spanning CNR1 and cannabis dependence in 1,923 individuals. Two SNPs that were previously associated with cannabis dependence in other studies were also significant with this phenotype in our analyses [rs806368 (P = 0.05) and rs806380 (P = 0.009)]. Haplotype analyses revealed the association to be largely driven by the SNP rs806380. These results suggest a role for the cannabinoid receptor 1 gene in cannabis dependence.
对大麻使用障碍的基因组学研究一直很有限。位于6号染色体q14 - 15区域的大麻素受体1基因(CNR1)是大麻依赖的一个极佳候选基因,因为该基因编码的G蛋白偶联受体在Δ9 - 四氢大麻酚的奖赏效应中发挥着重要作用。先前的研究发现,CNR1基因单核苷酸多态性(SNP)与物质使用障碍的总体易感性之间的关联证据并不明确。我们在1923名个体中研究了跨越CNR1基因的9个SNP与大麻依赖之间的关联。在我们的分析中,之前在其他研究中与大麻依赖相关的两个SNP也与该表型显著相关[rs806368(P = 0.05)和rs806380(P = 0.009)]。单倍型分析表明,这种关联在很大程度上是由SNP rs806380驱动的。这些结果表明大麻素受体1基因在大麻依赖中发挥作用。