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重大的社会代价，因为它们影响到如此多的儿童及其家庭，它们往往持续到青春期和成年期，其影响波及儿童的许多领域。年代的生活。了解这些问题的遗传和环境根源对于预测和预防这些问题至关重要。自1995年以来，MRC项目拨款G500079为英国双胞胎早期发展研究（TEDS）提供了持续的支持，研究儿童时期学习困难和相关行为问题的遗传学。这是美国最大的一项对双胞胎从婴儿期到青春期进行评估的研究。TEDS的发现为思考儿童时期学习困难和行为问题的遗传和环境根源提供了新的思路，其中最引人注目的是？多面手的基因吗?学习困难理论。这些发现为分子遗传学研究指明了方向，这些研究已经开始确定对这些疾病产生重大遗传影响的基因。在2010- 2015年期间，我们将利用这个为期15年的研究项目，对5000对16岁的孩子进行评估。16岁是社会和生物学发展的关键转折点，因为它即将结束义务教育，接近青春期结束。使用作为TEDS的一部分开发的基于网络的测试，我们将测试双胞胎的学习方面，这些方面在我们的研究中被证明是最重要和最有趣的：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使我们能够提出关于发育的关键问题（例如，遗传效应是否随着年龄的变化而变化？），关于疾病之间的联系（例如，不同的基因是否影响不同的疾病，如阅读和数学？），以及基因与环境之间的相互作用（例如，基因是否影响我们的经历？）。通过在4000名TEDS儿童身上获得200万个DNA标记，TEDS增加了巨大的价值，这将首次有可能在整个基因组中进行系统搜索，寻找导致这些遗传效应的基因。找到这些基因将有可能在儿童在学校表现不佳之前就识别出有风险的儿童，并促进环境干预措施，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.