The Mind Research Network, 1101 Yale Blvd NE, Albuquerque, NM 87106, USA.
J Abnorm Child Psychol. 2011 Jul;39(5):671-81. doi: 10.1007/s10802-011-9511-9.
Evidence for shared heritable influences across domains of substance use suggests that some genetic variants influence broad risk for externalizing behaviors. Theories of externalizing psychopathology also suggest that genetic liability for substance use manifests as temperamental risk factors, particularly those related to behavioral disinhibition, during adolescence. The cholinergic muscarinic receptor 2 gene (CHRM2) is a promising candidate for studying genetic influences on broad-based risk for externalizing traits. This study examined a candidate CHRM2 polymorphism (rs1455858) in relation to substance use and personality measures of disinhibition in a sample of high-risk adolescents (n = 124). Bivariate analyses and structural equation modeling (SEM) evaluated associations of rs1455858 with measures of drug involvement (alcohol, tobacco and marijuana) and disinhibition (indexed by impulsivity and sensation seeking scores). Bivariate analyses showed significant associations of CHRM2 with several behavioral phenotypes. In SEM analyses CHRM2 related significantly to latent measures of substance use and disinhibition; additionally, disinhibition mediated the association of CHRM2 with substance use. These results suggest that CHRM2 variants are potentially relevant for adolescent substance use and that temperamental risk factors could contribute to these associations.
物质使用领域中共享遗传影响的证据表明，某些遗传变异会影响外在行为的广泛风险。外在精神病理学理论还表明，物质使用的遗传易感性表现为青少年时期的气质风险因素，特别是与行为抑制解除相关的因素。胆碱能毒蕈碱受体 2 基因 (CHRM2) 是研究广泛外在特质遗传影响的有前途的候选基因。本研究在高危青少年样本中（n=124），研究了候选 CHRM2 多态性（rs1455858）与物质使用和抑制性人格测量之间的关系。双变量分析和结构方程模型 (SEM) 评估了 rs1455858 与药物使用（酒精、烟草和大麻）和抑制性（冲动性和感觉寻求得分指数）的关联。双变量分析显示 CHRM2 与多种行为表型存在显著关联。在 SEM 分析中，CHRM2 与物质使用和抑制的潜在测量值显著相关；此外，抑制性在 CHRM2 与物质使用的关联中起中介作用。这些结果表明，CHRM2 变体可能与青少年物质使用有关，而气质风险因素可能促成这些关联。
