Epigenetic trajectories of biological response to adolescent psychosocial stress: A novel longitudinal study of discordant monozygotic twins

对青少年社会心理压力的生物反应的表观遗传轨迹：一项针对不一致同卵双胞胎的新颖纵向研究

• 批准号: ES/N000277/1
• 负责人: Chloe Chung Yi Wong
• 金额: $ 51.08万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=ES%2FN000277%2F1
• 关键词: Epigenetic; trajectories; biological; response; adolescent

Stress is a normal, adaptive response to stressors (e.g. events that make a person feel threatened or upset) in our environment. However extensive research on the biology of stress now shows that healthy development can be derailed by excessive or prolonged activation of stress response systems in the body especially during important developmental periods in life such as adolescence. Exposure to severe stress during early life unfortunately is not uncommon. A World Health Organization survey reported that nearly 40% of adults experienced some form of severe stress during childhood and adolescence. Exposure to severe stress may have immediate or long lasting damaging effects on learning, behavior, and health. Therefore, it is imperative that we develop a better understanding of how exposure to psychosocial stress during adolescence gets under the skin to leave lasting biological imprints. There is now increasing evidence to show that one of the ways in which severe psychosocial stress exposure can lead to physical and emotional problems is by getting underneath the skin and influencing the degree to which genes are turned on and off. This regulation of gene expression is known as epigenetics and often occurs through changes in DNA methylation. Initial studies have shown that individuals exposed to severe psychosocial stress have different patterns of DNA methylation (epigenetic 'signatures') compared to individuals exposed to no/minimal stressful life events. However limited conclusions can be drawn from these studies as they often do not fully account for factors that are important in one's reactivity to stress including age, sex and genetic difference between individuals.Taking advantage of an established longitudinal twin study, our team of biological and social science experts will investigate epigenetic differences within 100 genetically identical twin pairs that exposed to different level of severe psychosocial stress during adolescence. In particular, all of these carefully selected twin pairs were not exposed to any major psychosocial stressors during childhood but in adolescence one twin is exposed to severe psychosocial stress while the co-twin is not. Severe psychosocial stress includes being physically attacked, beaten by parent, frequently bullied, sexually assaulted, persistently harassed on the internet or via a mobile phone, witnessing domestic violence, having a serious illness and being involved in an accident (e.g., a car accident). The use of genetically identical twins who essentially have the same genes and family experiences as well as age and sex will allow us to ascertain the 'purer' impact of psychosocial stress on the epigenetic signatures. Utilising repeated assessments over time (i.e. before and after exposure to stress) is a powerful design as it enables exploration of changes that occur within the same child rather than simply comparing one child to another. We will also investigate whether these stress-associated epigenetic signatures are similar or different in DNA extracted from cheek swabs and blood as this will help us to know whether these 'signatures' can be detected using minimally invasive procedures. The findings from this study will shed light on how biological systems operate under environmental challenge with the potential to ultimately advance understanding of how to sustain lifelong health and wellbeing and prevent health inequalities through early detection of the biological impact of psychosocial stress exposure which will aid prevention efforts. In addition, our multidisciplinary team is highly committed to increase awareness about epigenetics and how the environment may influence the way our genes are expressed and ultimately impact upon cognition and behaviour. This will be achieved through our team's ongoing public engagement with schools and science open days, as well as hosting workshops for university students across London.

压力是对我们环境中的压力源（例如使人感到威胁或不安的事件）的正常适应性反应。然而，对压力生物学的广泛研究现在表明，健康的发展可以通过过度或长期激活体内的压力反应系统而脱轨，特别是在生命中的重要发育时期，如青春期。不幸的是，在早期生活中暴露于严重的压力并不罕见。世界卫生组织的一项调查报告称，近40%的成年人在童年和青春期经历过某种形式的严重压力。暴露于严重的压力可能会对学习，行为和健康产生直接或长期的破坏性影响。因此，我们必须更好地了解青少年时期暴露于心理社会压力如何进入皮肤，留下持久的生物印记。现在有越来越多的证据表明，严重的心理社会压力暴露可能导致身体和情感问题的方式之一是通过进入皮肤下面并影响基因开启和关闭的程度。这种基因表达的调节被称为表观遗传学，通常通过DNA甲基化的变化发生。最初的研究表明，与没有/最小压力的生活事件相比，暴露于严重心理社会压力的个体具有不同的DNA甲基化模式（表观遗传“签名”）。然而，从这些研究中可以得出有限的结论，因为它们往往没有充分考虑到对一个人的压力反应的重要因素，包括年龄，性别和个体之间的遗传差异。我们的生物和社会科学专家小组将调查100对遗传相同的双胞胎的表观遗传差异，这些双胞胎暴露在不同程度的严重青春期的心理压力特别是，所有这些精心挑选的双胞胎在童年时期都没有受到任何重大的心理压力，但在青春期，双胞胎中的一个受到严重的心理压力，而双胞胎中的另一个则没有。严重的心理社会压力包括身体受到攻击，被父母殴打，经常被欺负，性侵犯，在互联网上或通过移动的电话持续骚扰，目睹家庭暴力，患有严重疾病和卷入事故（例如，车祸）。使用基因完全相同的双胞胎，他们基本上拥有相同的基因和家庭经历，以及年龄和性别，这将使我们能够确定心理社会压力对表观遗传特征的“更纯粹”的影响。随着时间的推移（即暴露于压力之前和之后）使用重复评估是一种强大的设计，因为它可以探索同一个孩子发生的变化，而不是简单地将一个孩子与另一个孩子进行比较。我们还将调查这些与压力相关的表观遗传特征在从脸颊拭子和血液中提取的DNA中是否相似或不同，因为这将有助于我们了解这些“特征”是否可以使用微创程序检测到。这项研究的结果将揭示生物系统如何在环境挑战下运作，并有可能最终促进对如何维持终身健康和福祉的理解，并通过早期发现心理社会压力暴露的生物影响来预防健康不平等，这将有助于预防工作。此外，我们的多学科团队高度致力于提高对表观遗传学的认识，以及环境如何影响我们基因的表达方式，并最终影响认知和行为。这将通过我们的团队与学校和科学开放日的持续公众参与，以及为伦敦的大学生举办研讨会来实现。

项目成果

A methylome-wide association study of major depression with out-of-sample case-control classification and trans-ancestry comparison

• DOI: 10.1101/2023.10.27.23297630
• 发表时间: 2023-10
• 作者: Xueyi Shen;M. Barbu;D. Caramaschi;R. Arathimos;D. Czamara;F. David;Anna Dearman;Evelyn Dilkes;Marisol Herrera-Rivero;F. Huider;L. Kühn;Kuan-Chen Lu;T. Palviainen;A. Schowe;Gemma L Shireby;Antoine Weihs;Chloe C. Y. Wong;E. Davyson;Hannah Casey;Mark J Adams;Antje-Kathrin Allgaier;Michael Barber;Joe Burrage;A. Caspi;Ricardo Costeira;Erin C. Dunn;L. Feldmann;J. Frank;F. Freisleder;D. Gadd;E. Greimel;E. Hannon;Sarah E Harris;G. Homuth;D. M. Howard;S. Iurato;T. Korhonen;Tzu-Pin Lu;N. G. Martin;Jade Martins;E. Mcdermott;S. Meinert;P. Navarro;M. Ollikainen;Verena Pehl;C. Piechaczek;A. D. Scherff;F. Stein;F. Streit;A. Teumer;H. Völzke;J. Dongen;R. Walker;Natan Yusupov;L. Arseneault;Jordana T. Bell;Klaus Berger;E. Binder;D. Boomsma;Simon R Cox;U. Dannlowski;K. Evans;Helen L. Fisher;A. Forstner;Hans‐Jörgen Grabe;J. Kaprio;T. Kircher;Johannes Kopf-Beck;M. Kumari;Po-Hsiu Kuo;Qingqin S. Li;T. Moffitt;Hugh Mulcahy;Therese M. Murphy;Gerd Schulte-Körne;J. Mill;C. Lewis;Optima Working Group;Pgc Mdd;N. Wray;Andrew M. McIntosh

DNA methylation signatures of adolescent victimization: analysis of a longitudinal monozygotic twin sample.

• DOI: 10.1080/15592294.2020.1853317
• 发表时间: 2021-11
• 期刊: Epigenetics
• 影响因子: 3.7
• 作者: Kandaswamy R;Hannon E;Arseneault L;Mansell G;Sugden K;Williams B;Burrage J;Staley JR;Pishva E;Dahir A;Roberts S;Danese A;Mill J;Fisher HL;Wong CCY
• 通讯作者: Wong CCY

Can epigenetics shine a light on the biological pathways underlying major mental disorders?

• DOI: 10.1017/s0033291721005559
• 发表时间: 2022-07
• 期刊: PSYCHOLOGICAL MEDICINE
• 影响因子: 6.9
• 作者: Alameda, Luis;Trotta, Giulia;Quigley, Harriet;Rodriguez, Victoria;Gadelrab, Romayne;Dwir, Daniella;Dempster, Emma;Wong, Chloe C. Y.;Forti, Marta Di
• 通讯作者: Forti, Marta Di

Patterns of Reliability: Assessing the Reproducibility and Integrity of DNA Methylation Measurement

• DOI: 10.1016/j.patter.2020.100014
• 发表时间: 2020-05-08
• 期刊: PATTERNS
• 影响因子: 6.5
• 作者: Sugden, Karen;Hannon, Eilis J.;Caspi, Avshalom
• 通讯作者: Caspi, Avshalom