Lu Ake T, Ogdie Matthew N, Järvelin Marjo-Ritta, Moilanen Irma K, Loo Sandra K, McCracken James T, McGough James J, Yang May H, Peltonen Leena, Nelson Stanley F, Cantor Rita M, Smalley Susan L
Department of Human Genetics, University of California, Los Angeles, California, USA.
Am J Med Genet B Neuropsychiatr Genet. 2008 Dec 5;147B(8):1488-94. doi: 10.1002/ajmg.b.30693.
Attention deficit hyperactivity disorder (ADHD) is a highly heritable disorder affecting some 5-10% of children and 4-5% of adults. The cannabinoid receptor gene (CNR1) is a positional candidate gene due to its location near an identified ADHD linkage peak on chromosome 6, its role in stress and dopamine regulation, its association with other psychiatric disorders that co-occur with ADHD, and its function in learning and memory. We tested SNP variants at the CNR1 gene in two independent samples-an unselected adolescent sample from Northern Finland, and a family-based sample of trios (an ADHD child and their parents). In addition to using the trios for association study, the parents (with and without ADHD) were used as an additional case/control sample of adults for association tests. ADHD and its co-morbid psychiatric disorders were examined. A significant association was detected for a SNP haplotype (C-G) with ADHD (P = 0.008). A sex by genotype interaction was observed as well with this haplotype posing a greater risk in males than females. An association of an alternative SNP haplotype in this gene was found for post-traumatic stress disorder (PTSD) (P = 0.04 for C-A, and P = 0.01 for C-G). These observations require replication, however, they suggest that the CNR1 gene may be a risk factor for ADHD and possibly PTSD, and that this gene warrants further investigation for a role in neuropsychiatric disorders.
注意缺陷多动障碍（ADHD）是一种高度可遗传的疾病，影响着约5%至10%的儿童和4%至5%的成年人。大麻素受体基因（CNR1）是一个定位候选基因，原因在于它位于6号染色体上已确定的ADHD连锁峰附近，在应激和多巴胺调节中发挥作用，与其他与ADHD共病的精神疾病相关，以及在学习和记忆中起作用。我们在两个独立样本中检测了CNR1基因的单核苷酸多态性（SNP）变体——一个来自芬兰北部的未经过筛选的青少年样本，以及一个基于家庭的三联体样本（一个患有ADHD的儿童及其父母）。除了将三联体用于关联研究外，还将父母（有ADHD和无ADHD）作为额外的成人病例/对照样本进行关联测试。对ADHD及其共病的精神疾病进行了检查。检测到一个SNP单倍型（C-G）与ADHD存在显著关联（P = 0.008）。还观察到该单倍型存在性别与基因型的相互作用，在男性中比女性带来更大风险。在该基因中发现另一个SNP单倍型与创伤后应激障碍（PTSD）相关（C-A的P = 0.04，C-G的P = 0.01）。然而，这些观察结果需要重复验证，不过它们表明CNR1基因可能是ADHD以及可能是PTSD的一个风险因素，并且该基因在神经精神疾病中的作用值得进一步研究。
