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

“新兴的成年期”，青春期和成熟的成年期之间的生命历程阶段，是年轻人离开家，在世界上走自己的路，过渡到独立的时候;一个脆弱的，多能的时间，可能是终身心理健康问题的“临界点”。我们将把遗传和基因组策略结合起来，以确定成年期认知和心理健康问题的遗传、环境和发育根源。我们的样本是独一无二的，由双胞胎成员组成，他们从婴儿期起就接受了双胞胎早期发育研究（TEDS）的纵向评估，该研究一直由MRC项目赠款（G0901245、G0500079、G9424799）。这是有史以来最大规模的纵向双胞胎研究。双胞胎设计可以从纯粹的环境影响中分离出遗传因素，婴儿期到青春期的数据，包括全基因组基因型，提供了一个发展框架，可以识别行为，遗传和环境风险/保护因素，预测成年后的好与坏结果。我们提出的研究有两个目标：目标1。确定行为，遗传和环境风险/保护因素，预测好与坏的结果在成年初。我们将评估一个英国代表性的10,000对21岁的TEDS双胞胎（5,000对）的广泛认知功能（例如，识字和算术），心理健康（例如，焦虑和幸福感）和环境测量（例如，情感支持和生活事件）与我们过去20年评估中使用的电池相当，以及针对成年期的新措施。这将使我们能够在正常发育的背景下，将TEDS的纵向遗传敏感数据集用于成年期的认知和心理健康问题。我们还将对5,000名无关参与者（双胞胎中的一员）和2,500名非同卵双胞胎进行全基因组基因分型，对数百万个DNA标记进行基因组分析;这些资源将使仅基于DNA的尖端基因组分析成为可能。目标2.识别出低智商个体在成年期出现的好与坏结果的预测因素。在最近的分子遗传学研究中，诊断出的智力残疾（<70 IQ）受到了很多关注，但对低IQ（70-79 IQ）知之甚少，这是常见的十倍，也导致了重大的个人和社会成本，特别是在日益技术化的世界中，在成年期的转折点。对于目标2，我们将调查年轻人在世界上闯出自己的路时所面临的认知挑战问题。我们的工作将产生第一个关于低智商对成年期适应影响的遗传敏感性研究，通过亲自评估600名21岁时智商得分为70-79的TEDS个体（400对双胞胎中至少有一名低智商先证者），来自不一致对的双胞胎，以及200名对照。我们将进行密集的面对面访谈，重点关注这些低智商个体及其孪生兄弟的适应功能和调整，因为他们开始在一个认知负担沉重的成人世界中前进。他们的结果将与以同样方式评估的200名TEDS个体的代表性对照样本进行比较。除了描述低智商个体进入成年后的结果外，我们还将使用双胞胎设计比较同卵和异卵双胞胎，首次调查低智商结果的遗传和环境起源。确定成年期认知和心理健康问题的遗传和环境根源，并追踪其发展根源，是预测和预防这些问题的基本步骤。

'Emerging adulthood', the phase of the life course between adolescence and full-fledged adulthood, is when young people transition to independence as they leave home and make their own way in the world; a vulnerable, pluripotent time that can be a 'tipping point' for life-long mental health problems. We will bring together genetic and genomic strategies in order to establish the genetic, environmental and developmental origins of cognitive and mental health problems in emerging adulthood.Our sample is unique, consisting of members of twin pairs who have been assessed longitudinally since infancy as part of the Twins Early Development Study (TEDS), which has been continuously funded by MRC programme grants (G0901245, G0500079, G9424799) since 1995. This is the largest ever in-depth longitudinal twin study. The twin design can disentangle genetic from purely environmental influences, and the infancy-through-adolescence data, including genome-wide genotypes, offer a developmental framework that can identify behavioural, genetic and environmental risk/protective factors that predict good vs poor outcomes in emerging adulthood.Our proposed research has two objectives: Objective 1. Identify behavioural, genetic and environmental risk/protective factors that predict good vs poor outcomes in emerging adulthood. We will assess a UK-representative sample of 10,000 TEDS twins (5,000 pairs) at age 21 on a broad battery of cognitive functioning (e.g., literacy and numeracy), mental health (e.g., anxiety and well-being) and environmental measures (e.g., emotional support and life events) comparable to the batteries used in our previous 20 years of assessment, as well as new measures specific to emerging adulthood. This will allow us to bring the longitudinal, genetically sensitive dataset of TEDS to bear on cognitive and mental health problems in emerging adulthood in the context of normal development. We will also conduct genomic analyses using genome-wide genotyping of millions of DNA markers for 5,000 unrelated participants (one member of a twin pair) and for 2,500 non-identical twins of these individuals; these resources will enable cutting-edge genomic analyses based on DNA alone. Objective 2. Identify predictors of good vs poor outcomes for individuals of low IQ in emerging adulthood. Diagnosed intellectual disability (<70 IQ) has received much attention in recent molecular genetics research, but little is known about low IQ (70-79 IQ), which is ten times more common and which also results in major personal and societal costs, especially during the tipping point of emerging adulthood in an increasingly technological world. For Objective 2, we will investigate the problems faced by young adults who are challenged cognitively as they make their own way in the world. Our work will yield the first genetically sensitive study of the effects of low IQ on adjustment in emerging adulthood, by assessing in person 600 TEDS individuals with 70-79 IQ scores at age 21 (members of 400 twin pairs with at least one low-IQ proband), co-twins from discordant pairs, and 200 controls. We will conduct intensive in-person interviews focused on the adaptive functioning and adjustment of these low-IQ individuals and their co-twins as they begin to make their way in a cognitively taxing adult world. Their outcomes will be compared to a representative control sample of 200 TEDS individuals assessed in the same way. In addition to describing outcomes for individuals with low IQ as they emerge into adulthood, we will use the twin design comparing identical and non-identical twins to investigate, for the first time, the genetic and environmental origins of these outcomes of low IQ. Identifying the genetic and environmental origins of cognitive and mental health problems in emerging adulthood and tracing their developmental roots is a fundamental step towards predicting and preventing these problems.