SGDP Research Centre, Institute of Psychiatry, Kings College, London, UK.
Genes Brain Behav. 2010 Apr;9(3):296-304. doi: 10.1111/j.1601-183X.2009.00560.x. Epub 2009 Dec 17.
It is well known that there are strong genetic influences on attention-deficit hyperactivity disorder (ADHD), with genetic association studies providing good evidence for the involvement of the dopamine neurotransmitter system in its aetiology. Developmental origins of ADHD represent an interesting area of research to understand the genetics that underlie early appearing individual differences. However, understanding the molecular basis of ADHD requires accurate, unbiased, heritable measures that can be used for molecular genetic association analyses. We take two approaches to examine the genetics of ADHD behaviours in infancy. Using quantitative genetic techniques, we explore the relationship between objective measures of activity level (AL) in both home and laboratory environments as well as with parent ratings of ADHD symptoms in a population sample of 2-year-old twins. Molecular association analyses of these measures examine candidate genes previously associated with ADHD. We find that ADHD symptoms, AL in the home and AL in the lab represent heritable phenotypes in 2-year-old infants. AL measured in the home has a strong genetic correlation with symptoms of ADHD, whereas AL in the lab correlates only modestly with the same ADHD measure. Genetic correlations suggest that AL in the home is more comparable than AL in the lab to ADHD behaviour and support the separation of all three for molecular analyses. There was modest evidence for association between DAT1, NET1 and ADHD symptom scores, as well as between DAT1 and AL in the lab.
众所周知,注意力缺陷多动障碍(ADHD)受强烈遗传因素的影响,遗传关联研究为多巴胺神经递质系统在其发病机制中的作用提供了充分的证据。ADHD 的发育起源是理解潜在遗传因素的一个有趣的研究领域,这些遗传因素导致了早期出现的个体差异。然而,了解 ADHD 的分子基础需要使用准确、无偏、可遗传的方法来进行分子遗传关联分析。我们采用两种方法来研究婴儿期 ADHD 行为的遗传学。使用定量遗传学技术,我们在一个 2 岁双胞胎的人群样本中,探索了活动水平(AL)的客观测量值在家庭和实验室环境中的关系,以及与 ADHD 症状的父母评分之间的关系。对这些措施的分子关联分析检查了先前与 ADHD 相关的候选基因。我们发现,ADHD 症状、家庭中的 AL 和实验室中的 AL 在 2 岁婴儿中是可遗传的表型。家庭中测量的 AL 与 ADHD 症状有很强的遗传相关性,而实验室中的 AL 仅与相同的 ADHD 测量值有适度的相关性。遗传相关性表明,家庭中的 AL 与 ADHD 行为更可比,并且支持将三者全部用于分子分析。在 DAT1、NET1 和 ADHD 症状评分之间,以及在 DAT1 和实验室中的 AL 之间,有中度的关联证据。