Intellectual Disability and Mental Health: Assessing Genomic Impact on Neurodevelopment (IMAGINE)

智力障碍和心理健康:评估基因组对神经发育的影响(IMAGINE)

基本信息

  • 批准号:
    MR/N022572/1
  • 负责人:
  • 金额:
    $ 324.73万
  • 依托单位:
  • 依托单位国家:
    英国
  • 项目类别:
    Research Grant
  • 财政年份:
    2016
  • 资助国家:
    英国
  • 起止时间:
    2016 至 无数据
  • 项目状态:
    已结题

项目摘要

In 2013, there were 1.1 million people with intellectual disabilities (ID) in England; 224,930 were children of school age. Although the cause of such disability can be events such as extreme prematurity or brain infections, genetic factors could account for 85%. Some genetic risk is inherited, but not all. Recent research has shown that, during the formation of the egg or sperm, minor chromosomal structural anomalies can occur. They are known as copy number variations (CNVs). The most serious CNVs are not present in either parent, but are 'newly occurring'. Fortunately, these are rare events, but if they occur in key regions of our genome they are strongly associated with ID. Nowadays, the cost of examining a patient's DNA for CNV is coming down dramatically. In the UK nearly all children with ID presenting to paediatric services have the test. The National Health Service (NHS) pays, and reports are stored in the UK Regional Genetics Centres (RGC).In 10-15% the test reveals a CNV that is probably the cause of ID. Up to 45,000 people each year have these tests. Consequently, there is an enormous wealth of information about CNV held within UK RGC. Knowing that a particular CNV may cause ID is valuable, but ID is commonly associated with severe behavioural and emotional problems too. In adult life, many individuals with ID go on to have more serious mental illness, such as schizophrenia. We do not currently understand why these problems develop in some people with ID but not in others. When a clinically significant CNV is found in a child with ID, families deserve to be told what the future holds for that child, and how they should best manage behavioural and educational issues to avert poor mental health outcomes. Our unique and novel programme of research aims to rectify that deficiency. Our main objective is to create a novel and comprehensive genetic knowledge base, incorporating a wide range of rare CNV, linked to detailed information about the genetic anomaly's impact on adjustment in childhood and adulthood. We have spent the past year testing the feasibility of our MRC-funded research strategy, and have achieved all our objectives. We are now embarking on a further 3.5 year programme of research to build on the infrastructure we have created. Our IMAGINE legacy resource will be accessible to clinicians managing people with ID, not only in the UK but also around the world, and its establishment will benefit people with ID and their families throughout the lifespan. In one workstream, we are drawing on the opportunity offered by the NHS-based resource of CNV reports. We will focus on behavioural adjustment in childhood, and aim to recruit around 5,000 families nationally. We have shown that it is possible to obtain parent reports about behaviour and abilities of children online, or by telephone, using well-tested measures of behavioural adjustment, social circumstances and medical history. Families are enthusiastic to tell us about their children and they value the reports we send them, following completion of our online assessments. These provide a useful summary for schools and clinicians alike.In the other workstream, the focus is on a few relatively common CNV that are associated with a particularly high risk of poor mental health in adulthood. We select children with the designated CNVs from the national study, study their abilities and their adjustment by home-based assessments,. We will assess the severity of emotional and behavioural problems, and the importance of environmental risks, such as parental mental health, ethnicity or poverty. We will also recruit adults with ID who possess the same relatively common CNVs, to study long-term outcomes. In this way we aim to discover, for the first time, how the risk attaching to these important CNV manifests in childhood and adulthood, and potentially identify points for intervention to ameliorate that risk.
2013年,英国有110万智障人士;其中224,930人为学龄儿童。虽然这种残疾的原因可能是极端早产或脑部感染等事件,但遗传因素可能占85%。一些遗传风险是遗传的,但不是全部。最近的研究表明,在卵子或精子的形成过程中,可能会发生轻微的染色体结构异常。它们被称为拷贝数变异(CNV)。最严重的CNV并不存在于父母双方身上,而是“新近发生”。幸运的是,这些都是罕见的事件,但如果它们发生在我们基因组的关键区域,它们与ID密切相关。如今,检查患者DNA中CNV的成本正在大幅下降。在英国,几乎所有向儿科服务机构出示身份证的儿童都要进行这项测试。英国国家医疗服务体系(NHS)支付费用,报告存储在英国区域遗传学中心(RGC)。在10%-15%的测试中,CNV可能是导致ID的原因。每年有多达4.5万人接受这类测试。因此,英国研资局拥有大量关于CNV的信息。知道一种特定的CNV可能导致ID是有价值的,但ID通常也与严重的行为和情感问题有关。在成年生活中,许多患有智障的人会患上更严重的精神疾病,如精神分裂症。我们目前不明白为什么这些问题在一些ID患者身上出现,而在另一些人身上没有。当发现具有临床意义的CNV时,应该告诉家庭该儿童的未来是什么,以及他们应该如何最好地管理行为和教育问题,以避免不良的心理健康结果。我们独特和新颖的研究方案旨在纠正这一不足。我们的主要目标是创建一个新颖和全面的遗传知识库,纳入广泛的罕见CNV,与关于遗传异常对儿童和成年适应的影响的详细信息相联系。在过去的一年里,我们一直在测试我们由MRC资助的研究战略的可行性,并实现了我们的所有目标。我们现正展开另一项为期3.5年的研究计划,以期在我们已建立的基础设施基础上再接再厉。不仅在英国,而且在世界各地,管理ID患者的临床医生都可以访问我们的Imagine遗产资源,它的建立将使ID患者及其家人终身受益。在一个工作流程中,我们正在利用基于NHS的CNV报告资源提供的机会。我们将专注于儿童时期的行为调整,目标是在全国范围内招募约5000个家庭。我们已经证明,使用经过充分测试的行为调整、社会环境和病史等措施,可以在网上或通过电话获得关于儿童行为和能力的父母报告。家庭都很热情地告诉我们他们孩子的情况,在我们完成在线评估后,他们很重视我们给他们发送的报告。这些为学校和临床医生提供了有用的总结。在另一种工作流程中,重点放在几个相对常见的CNV上,这些CNV与成年后精神健康不良的风险特别高有关。我们从国家研究中选择有指定CNV的儿童,通过家庭评估来研究他们的能力和适应。我们将评估情绪和行为问题的严重性,以及环境风险的重要性,例如父母的精神健康、种族或贫困。我们还将招募具有相同相对常见CNV的ID成人,以研究长期结果。通过这种方式,我们的目标是首次发现与这些重要的CNV相关的风险如何在儿童和成人中表现出来,并潜在地确定改善这种风险的干预点。

项目成果

期刊论文数量(9)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Using induced pluripotent stem cells to investigate human neuronal phenotypes in 1q21.1 deletion and duplication syndrome
使用诱导多能干细胞研究 1q21.1 缺失和重复综合征中的人类神经元表型
  • DOI:
    10.1101/2021.02.08.430246
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Chapman G
  • 通讯作者:
    Chapman G
Behavioural and neurodevelopmental characteristics of SYNGAP1
SYNGAP1 的行为和神经发育特征
  • DOI:
    10.21203/rs.3.rs-3722732/v1
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Bednarczuk N
  • 通讯作者:
    Bednarczuk N
Using induced pluripotent stem cells to investigate human neuronal phenotypes in 1q21.1 deletion and duplication syndrome.
  • DOI:
    10.1038/s41380-021-01182-2
  • 发表时间:
    2022-03
  • 期刊:
  • 影响因子:
    11
  • 作者:
    Chapman, Gareth;Alsaqati, Mouhamed;Lunn, Sharna;Singh, Tanya;Linden, Stefanie C.;Linden, David E. J.;van den Bree, Marianne B. M.;Ziller, Mike;Owen, Michael J.;Hall, Jeremy;Harwood, Adrian J.;Syed, Yasir Ahmed
  • 通讯作者:
    Syed, Yasir Ahmed
Sleep disturbance as a transdiagnostic marker of psychiatric risk in children with neurodevelopmental risk genetic conditions
睡眠障碍作为神经发育风险遗传性疾病儿童精神风险的跨诊断标志
  • DOI:
    10.21203/rs.3.rs-1922492/v1
  • 发表时间:
    2022
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Chawner S
  • 通讯作者:
    Chawner S
Beyond the Global Brain Differences: Intraindividual Variability Differences in 1q21.1 Distal and 15q11.2 BP1-BP2 Deletion Carriers.
  • DOI:
    10.1016/j.biopsych.2023.08.018
  • 发表时间:
    2024-01-15
  • 期刊:
  • 影响因子:
    10.6
  • 作者:
    Boen R;Kaufmann T;van der Meer D;Frei O;Agartz I;Ames D;Andersson M;Armstrong NJ;Artiges E;Atkins JR;Bauer J;Benedetti F;Boomsma DI;Brodaty H;Brosch K;Buckner RL;Cairns MJ;Calhoun V;Caspers S;Cichon S;Corvin AP;Crespo-Facorro B;Dannlowski U;David FS;de Geus EJC;de Zubicaray GI;Desrivières S;Doherty JL;Donohoe G;Ehrlich S;Eising E;Espeseth T;Fisher SE;Forstner AJ;Fortaner-Uyà L;Frouin V;Fukunaga M;Ge T;Glahn DC;Goltermann J;Grabe HJ;Green MJ;Groenewold NA;Grotegerd D;Grøntvedt GR;Hahn T;Hashimoto R;Hehir-Kwa JY;Henskens FA;Holmes AJ;Håberg AK;Haavik J;Jacquemont S;Jansen A;Jockwitz C;Jönsson EG;Kikuchi M;Kircher T;Kumar K;Le Hellard S;Leu C;Linden DE;Liu J;Loughnan R;Mather KA;McMahon KL;McRae AF;Medland SE;Meinert S;Moreau CA;Morris DW;Mowry BJ;Mühleisen TW;Nenadić I;Nöthen MM;Nyberg L;Ophoff RA;Owen MJ;Pantelis C;Paolini M;Paus T;Pausova Z;Persson K;Quidé Y;Marques TR;Sachdev PS;Sando SB;Schall U;Scott RJ;Selbæk G;Shumskaya E;Silva AI;Sisodiya SM;Stein F;Stein DJ;Straube B;Streit F;Strike LT;Teumer A;Teutenberg L;Thalamuthu A;Tooney PA;Tordesillas-Gutierrez D;Trollor JN;van 't Ent D;van den Bree MBM;van Haren NEM;Vázquez-Bourgon J;Völzke H;Wen W;Wittfeld K;Ching CRK;Westlye LT;Thompson PM;Bearden CE;Selmer KK;Alnæs D;Andreassen OA;Sønderby IE;ENIGMA-CNV Working Group
  • 通讯作者:
    ENIGMA-CNV Working Group
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David Skuse其他文献

Comparison of autism domains across thirty rare variant genotypes
三十种罕见变异基因型的自闭症领域比较
  • DOI:
    10.1016/j.ebiom.2024.105521
  • 发表时间:
    2025-02-01
  • 期刊:
  • 影响因子:
    10.800
  • 作者:
    Nabila M.H. Ali;Samuel J.R.A. Chawner;Leila Kushan-Wells;Carrie E. Bearden;Jennifer Gladys Mulle;Rebecca M. Pollak;Raquel E. Gur;Wendy K. Chung;Harriet Housby;Irene Lee;David Skuse;Jeanne Wolstencroft;William Mandy;Spiros Denaxas;Kate Baker;Lucy Raymond;Marianne van den Bree;Samuel Chawner;Jeremy Hall;Peter Holmans;Marianne B.M. van den Bree
  • 通讯作者:
    Marianne B.M. van den Bree
Atypical neurogenesis in induced pluripotent stem cell (iPSC)
诱导多能干细胞 (iPSC) 中的非典型神经发生
  • DOI:
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Dwaipayan Adhya;V. Swarup;R. Nagy;L. Dutan;C. Shum;K. Jozwik;Maria Andreina Mendez;J. Horder;P. Nowosiad;Irene O. Lee;David Skuse;F. Flinter;D. Murphy;G. McAlonan;Daniel H. Geschwind;Jack Price;J. Carroll;Simon Baron
  • 通讯作者:
    Simon Baron
Mental health and behavioural problems in children with XXYY: a comparison with intellectual disabilities
XXYY 儿童的心理健康和行为问题:与智力障碍的比较
Human Motor Neuron Diseases. Volume 36 of Advances in Neurology
人类运动神经元疾病。
Genomic imprinting of the X chromosome: a novel mechanism for the evolution of sexual dimorphism.
X 染色体的基因组印记:性二态性进化的新机制。

David Skuse的其他文献

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{{ truncateString('David Skuse', 18)}}的其他基金

IMAGINE-2: Stratifying Genomic Causes of Intellectual Disability by Mental Health Outcomes in Childhood and Adolescence
IMAGINE-2:根据儿童和青少年时期的心理健康结果对智力障碍的基因组原因进行分层
  • 批准号:
    MR/T033045/1
  • 财政年份:
    2020
  • 资助金额:
    $ 324.73万
  • 项目类别:
    Research Grant
Intellectual Disability and Mental Health: Assessing Genomic Impact on Neurodevelopment (IMAGINE)
智力障碍和心理健康:评估基因组对神经发育的影响(IMAGINE)
  • 批准号:
    MR/L011166/1
  • 财政年份:
    2014
  • 资助金额:
    $ 324.73万
  • 项目类别:
    Research Grant

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Women marginalised by mental health, disability or refugee status
因心理健康、残疾或难民身份而被边缘化的妇女
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IMAGINE-2: Stratifying Genomic Causes of Intellectual Disability by Mental Health Outcomes in Childhood and Adolescence
IMAGINE-2:根据儿童和青少年时期的心理健康结果对智力障碍的基因组原因进行分层
  • 批准号:
    MR/T033045/1
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    2020
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Development of a self-management program based on well-being theory for the people with mental disability
基于幸福理论的精神障碍者自我管理计划的开发
  • 批准号:
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Explaining symptom severity, distress and disability in chronic pain: The role of mental defeat
解释慢性疼痛的症状严重程度、痛苦和残疾:精神挫败的作用
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支持实施新的循证实践计划,促进精神残疾者出院并定居社区。
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