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

“新成年期”是指从青春期到成年期之间的人生阶段，是指年轻人离开家，在这个世界上走自己的路，向独立过渡；一个脆弱的多能期，可能成为终身精神健康问题的“引爆点”。我们将把遗传和基因组战略结合起来，以确定成年初期认知和心理健康问题的遗传、环境和发展根源。我们的样本是独特的，由双胞胎成员组成，他们从婴儿期开始就被纵向评估，作为双胞胎早期发展研究（TEDS）的一部分，该研究自1995年以来一直由MRC项目资助（G0901245, G0500079, G9424799）。这是有史以来规模最大的纵向双胞胎研究。双胞胎设计可以将基因与纯粹的环境影响分开，从婴儿到青春期的数据，包括全基因组基因型，提供了一个发育框架，可以识别行为、遗传和环境风险/保护因素，预测成年初期的好与坏结果。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，预测成年初期的好与坏结果。我们将评估一个具有英国代表性的样本，包括10000对21岁的TEDS双胞胎（5000对），包括认知功能（如识字和计算能力）、心理健康（如焦虑和幸福感）和环境措施（如情感支持和生活事件），这些措施与我们前20年评估中使用的电池相当，以及针对成年初期的新措施。这将使我们能够将TEDS的纵向、遗传敏感数据集用于研究正常发育背景下初成年期的认知和心理健康问题。我们还将对5000名不相关的参与者（双胞胎中的一个成员）和2500名这些个体的非同卵双胞胎进行基因组分析，使用数百万个DNA标记的全基因组基因分型；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。确定低智商个体在成年初期的好与坏结果的预测因素。在最近的分子遗传学研究中，被诊断为智力残疾（IQ <70）的人受到了很多关注，但对低智商（IQ 70-79）的人却知之甚少，低智商的人比低智商的人多十倍，而且还会导致重大的个人和社会成本，特别是在日益科技化的世界中，在即将成年的临界点期间。对于目标2，我们将调查年轻人面临的问题，他们在世界上自己的道路上受到认知挑战。通过对600名21岁时智商得分在70-79分的TEDS个体（400对至少有一个低智商先证者的双胞胎中的成员）、来自不一致双胞胎的同卵双胞胎和200名对照者进行评估，我们的工作将产生首个关于低智商对成年期适应影响的基因敏感研究。我们将进行密集的面对面访谈，重点关注这些低智商个体和他们的双胞胎在他们开始进入认知繁重的成人世界时的适应功能和调整。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成年后的结果外，我们还将使用双胞胎设计来比较同卵和异卵双胞胎，首次调查这些低智商结果的遗传和环境起源。确定成年初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.