Dick Danielle M, Latendresse Shawn J, Lansford Jennifer E, Budde John P, Goate Alison, Dodge Kenneth A, Pettit Gregory S, Bates John E
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Department of Psychiatry, PO Box 980126, Richmond, VA 23298-0126, USA.
Arch Gen Psychiatry. 2009 Jun;66(6):649-57. doi: 10.1001/archgenpsychiatry.2009.48.
As we identify genes involved in psychiatric disorders, the next step will be to study how the risk associated with susceptibility genes manifests across development and in conjunction with the environment. We describe analyses aimed at characterizing the pathway of risk associated with GABRA2, a gene previously associated with adult alcohol dependence, in a community sample of children followed longitudinally from childhood through young adulthood.
To test for an association between GABRA2 and trajectories of externalizing behavior from adolescence to young adulthood and for moderation of genetic effects by parental monitoring.
Data were analyzed from the Child Development Project, with yearly assessments conducted since that time. A saliva sample was collected for DNA at the 2006 follow-up, with a 93% response rate in the target sample. Growth mixture modeling was conducted using Mplus to identify trajectories of externalizing behavior and to test for effects of GABRA2 sequence variants and parental monitoring.
Nashville and Knoxville, Tennessee, and Bloomington, Indiana.
A community-based sample of families enrolled at 3 sites as children entered kindergarten in 1987 and 1988. Analyses for the white subset of the sample (n = 378) are reported here.
Parental monitoring measured at 11 years of age; Child Behavior Checklist youth reports of externalizing behavior at ages 12, 14, 15, 16, 17, 19, 20, 21, and 22 years.
Two classes of externalizing behavior emerged: a stable high externalizing class and a moderate decreasing externalizing behavior class. The GABRA2 gene was associated with class membership, with subjects who showed persistent elevated trajectories of externalizing behavior more likely to carry the genotype previously associated with increased risk of adult alcohol dependence. A significant interaction with parental monitoring emerged; the association of GABRA2 with externalizing trajectories diminished with high levels of parental monitoring.
These analyses underscore the importance of studying genetic effects across development and of identifying environmental factors that moderate risk.
随着我们确定与精神疾病相关的基因，下一步将是研究与易感基因相关的风险如何在整个发育过程中以及与环境共同作用下表现出来。我们描述了旨在刻画与GABRA2相关的风险途径的分析，GABRA2是一个先前与成人酒精依赖相关的基因，在一个从童年到青年期纵向跟踪的儿童社区样本中进行研究。
测试GABRA2与从青少年到青年期外化行为轨迹之间的关联，以及父母监督对遗传效应的调节作用。
对儿童发展项目的数据进行分析，自那时起每年进行评估。在2006年随访时收集唾液样本用于DNA检测，目标样本的应答率为93%。使用Mplus进行生长混合模型分析，以确定外化行为轨迹，并测试GABRA2序列变异和父母监督的影响。
田纳西州的纳什维尔和诺克斯维尔，以及印第安纳州的布卢明顿。
1987年和1988年儿童进入幼儿园时在3个地点招募的以社区为基础的家庭样本。这里报告了样本中白人子集（n = 378）的分析结果。
11岁时测量的父母监督；12、14、15、16、17、19、20、21和22岁时儿童行为检查表中青少年外化行为报告。
出现了两类外化行为：稳定的高外化行为类别和中度下降的外化行为类别。GABRA2基因与类别归属相关，表现出持续升高的外化行为轨迹的受试者更有可能携带先前与成人酒精依赖风险增加相关的基因型。出现了与父母监督的显著交互作用；随着父母监督水平的提高，GABRA2与外化轨迹的关联减弱。
这些分析强调了研究整个发育过程中的遗传效应以及确定调节风险的环境因素的重要性。
