Origins of learning difficulties and behaviour problems: from behavioural genetics to behavioural genomics

学习困难及其相关的行为问题造成了巨大的社会成本，因为它们影响着如此多的儿童和他们的家庭，往往会持续到青春期和成年期，其影响波及到儿童的许多领域--S生活。了解这些问题的遗传和环境根源对于预测和预防它们至关重要。自1995年以来，MRC项目赠款G500079一直为英国双胞胎早期发展研究(TEDS)提供持续支持，该研究涉及儿童学习困难及相关行为问题的遗传学，是世界上最大的双胞胎研究-S，对双胞胎从婴儿期到青春期进行评估。TEDS的发现为儿童学习困难和行为问题的遗传和环境根源带来了新的思考方式，最值得注意的是多面手基因？学习困难论。这些发现为分子遗传学研究绘制了道路，分子遗传学研究已经开始识别对这些疾病产生实质性遗传影响的基因。在2010-2015年间，我们将利用这项为期15年的研究计划，评估5000对16岁儿童，这是一个关键的社会和生物学发展转折点，就像义务教育结束和青春期接近结束时一样。使用作为TEDS的一部分开发的基于网络的测试，我们将测试这对双胞胎在我们的研究中被证明最重要和最有趣的学习方面：阅读、语言和演讲、数学、科学和一般认知能力。我们还将评估学校表现(GCSE)、行为问题以及家庭和学校环境。这项研究不仅仅是关于遗传在多大程度上影响学习困难及其相关问题的先天-后天问题。比较同卵双胞胎和异卵双胞胎的经典双胞胎设计让我们能够问一些关键问题，比如发育(例如，遗传效应是否会随着年龄的变化而改变？)，关于障碍之间的联系(例如，不同的基因是否会影响不同的障碍，如阅读和数学？)，以及基因和环境之间的相互作用(例如，基因是否会影响我们的体验？)。通过在4000名TEDS儿童中获得200万个DNA标记，TEDS获得了巨大的价值，这将使首次有可能在整个基因组中系统地搜索导致这些遗传效应的基因。发现这些基因将使人们有可能在儿童失学之前很久就发现他们处于危险之中，并促进环境干预，以防止这些疾病的发生。

Learning difficulties and their associated behaviour problems incur major social cost because they affect so many children and their families, they often persist into adolescence and adulthood, and their effects spill into many areas of children?s lives. Understanding the genetic and environmental origins of these problems is critical to predicting and preventing them. Since 1995, MRC programme grant G500079 has provided continuous support for the UK Twins Early Development Study (TEDS) on the genetics of learning difficulties and associated behaviour problems in childhood, the world?s largest study of twins assessed from infancy to adolescence. TEDS findings have led to new ways of thinking about the genetic and environmental origins of learning difficulties and behaviour problems in childhood, most notably a ?generalist genes? theory of learning difficulties. These findings have charted the course for molecular genetic research that has begun to identify genes responsible for the substantial genetic influence on these disorders. During 2010-15, we will capitalise on this 15-year programme of research by assessing 5000 pairs of at age 16, a crucial developmental turning point socially and biologically coming as it does at the end of compulsory education and near the end of puberty. Using Web-based tests that have been developed as part of TEDS, we will test the twins for aspects of learning that have proven most important and interesting in our research: reading, language and speech, mathematics, science, and general cognitive ability. We will also assess school performance (GCSE), behaviour problems, and home and school environments. This research is not merely about the nature-nurture issue of how much genetics affects learning difficulties and their associated problems. The classic twin design comparing identical and non-identical twins allows us to ask key questions about development (e.g., do genetic effects change from age to age?), about links between disorders (e.g., do different genes affect different disorders such as reading and mathematics?), and about the interplay between genes and environment (e.g., do genes affect our experiences?). Great value has been added to TEDS by obtaining two million DNA markers on 4000 of the TEDS children, which will make it possible for the first time to conduct systematic searches across the genome for genes responsible for these genetic effects. Finding these genes will make it possible to identify children at risk long before they fail in school and to foster environmental interventions that prevent the onset of these disorders.