Epigenetic, Telomere & Chromosome Changes in Adult Twins Having Child Adversity

表观遗传、端粒

• 批准号: 8726264
• 负责人: COLLEEN K JACKSON-COOK
• 金额: $ 6.25万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8726264
• 关键词: 8 year old; Adolescence; Adult; Adverse event; Age; Area; Base Sequence; Behavioral; Biological; Biological Assay; Biological Markers; Blood specimen; Cardiovascular Diseases; Cardiovascular system; Child; Child Sexual Abuse; Childhood; Chromosomal Instability; Chromosomes; Chromosomes, Human, Pair 2; Communicable Diseases; Coupling; DNA; Data; Databases; Development; Diabetes Mellitus; Disease; Dizygotic Twins; Environmental Exposure; Environmental Risk Factor; Epigenetic Process; Etiology; Evaluation; Event; Frequencies; Gene Expression; Gene Expression Alteration; Gene Expression Profile; Genetic Variation; Genomics; Goals; Health; Heritability; Human; Hydrocortisone; Illness impact; Individual; Investigation; Lead; Length; Life Stress; Location; Longevity; Malignant Neoplasms; Measures; Mediating; Mediator of activation protein; Memory; Methodology; Methods; Methylation; Monozygotic Twinning; Monozygotic twins; Morbidity - disease rate; Mutation; Outcome; Pathologic; Pattern; Phenotype; Population; Psychosocial Influences; Recording of previous events; Research; Research Personnel; Risk; Risk Factors; Salivary; Sampling; Severities; Sexual abuse; Source; Staging; Therapeutic Intervention; Treatment/Psychosocial Effects; Twin Multiple Birth; Twin Studies; Violence; age related; base; behavioral health; cohort; environmental stressor; epigenomics; experience; genome wide methylation; genome-wide; insight; meetings; mortality; neglect; population based; public health relevance; respiratory; response; social; telomere; young adult

DESCRIPTION (provided by applicant): Psychosocial influences have been implicated in the etiology of several of the most common illnesses impacting human health (cardiovascular disease; diabetes; cancer). It has been hypothesized that these psychosocial effects are mediated through DNA-based biological changes, such as methylation alterations or telomere attrition. However, due to the paucity of research in this area, many questions remain: To what extent do epigenetic and acquired genomic changes accumulate over the human lifespan? Do childhood adversities result in biological changes that persist into adulthood? Can an adult who was exposed to childhood adversities be identified as "at risk" for developing disease based on their epigenetic, gene expression, telomeric, chromosomal instability, and/or cortisol level profiles? To answer these questions we will study 736 twins who have completed intense phenotypic behavioral evaluations in previous studies (completed 2 to 15 years ago) and represent two risks groups: (1) twins experiencing the extreme childhood adversity event of sexual abuse; and (2) twins experiencing a broad spectrum of social experiences. Cohort 1 (ages 40-55) will comprise a selected sample of 50 identical twin pairs who are discordant for a history of childhood sexual abuse, as well as 50 identical concordant pairs who did (25 pairs) or did not (25 pairs) experience sexual abuse as a child. The biological endpoints that will be measured and compared between co-twins for this cohort include: (1) frequencies and locations of genome-wide methylation changes using a sequence-based approach; (2) chromosome-specific telomere lengths; (3) frequencies of acquired chromosomal instability; (4) patterns of gene expression; and (4) diurnal basal salivary cortisol levels. Cohort 2 (ages 20-30) will be comprised of a normative sample of monozygotic (157 pairs) and dizygotic (111 pairs) twin pairs for whom behavioral phenotypes have been carefully determined throughout adolescence into young adulthood. The data gained from the study of these twins will provide insight as to the potential cumulative effect of multiple adversities on embedded biological changes. The biological endpoints to be measured for this cohort (for whom blood samples have been previously collected and are readily available) include: (1) frequencies and locations of genome-wide methylation changes using array based methodology; and (2) gene expression patterns. Collectively, comparisons of observed alterations in biological endpoint measures (within and between twins) to phenotypic data collected from multiple stages in the human lifespan will allow us to deduce the extent to which the observed differences in biomarkers are influenced by childhood adversity, adult adversity, and/or other environmental stressors. The data from this investigation will lead to the first direct estimate of the frequency of epigenetic, telomere length, acquired chromosomal instability, gene expression, and/or cortisol level changes that arise in adults due to childhood adversities.

描述(由申请人提供)：心理社会影响与几种影响人类健康的最常见疾病(心血管疾病、糖尿病、癌症)的病因学有关。有人假设，这些心理社会效应是通过基于DNA的生物学变化来调节的，例如甲基化改变或端粒磨损。然而，由于这一领域研究的匮乏，许多问题仍然存在：表观遗传和获得性基因组变化在人类寿命中积累到什么程度？童年的逆境会导致持续到成年的生物变化吗？根据表观遗传学、基因表达、端粒、染色体不稳定和/或皮质醇水平的特征，暴露在童年逆境中的成年人能否被确定为罹患疾病的“风险”？为了回答这些问题，我们将研究736对双胞胎，他们在之前的研究中完成了激烈的表型行为评估(在2到15年前完成)，代表了两个风险群体：(1)经历过极端童年逆境事件的性虐待双胞胎；(2)经历过广泛社会经历的双胞胎。第一组(年龄40-55岁)将从50对不符合儿童期性虐待史的同卵双胞胎中挑选出来，以及50对在童年时经历过性虐待(25对)或没有(25对)经历过性虐待的完全一致的双胞胎。将在这一队列的同卵双胞胎之间进行测量和比较的生物终点包括：(1)使用基于序列的方法的全基因组甲基化变化的频率和位置；(2)染色体特定的端粒长度；(3)获得性染色体不稳定的频率；(4)基因表达的模式；以及(4)每日基础唾液皮质醇水平。第二组(年龄20-30岁)将由一对标准的单卵双胞胎(157对)和异卵双胞胎(111对)组成，这些双胞胎的行为表型在整个青春期到年轻成年期都得到了仔细的确定。从对这些双胞胎的研究中获得的数据将提供关于多重逆境对嵌入的生物变化的潜在累积影响的洞察力。该队列(其血液样本先前已采集并可随时获得)的生物终点包括：(1)使用基于阵列的方法进行全基因组甲基化改变的频率和位置；以及(2)基因表达模式。总而言之，将观察到的生物终点测量的变化(双胞胎内部和双胞胎之间)与从人类寿命的多个阶段收集的表型数据进行比较，将使我们能够推断观察到的生物标记物的差异受童年逆境、成人逆境和/或其他环境应激因素影响的程度。这项研究的数据将导致第一次直接估计由于童年逆境而在成人中出现的表观遗传学、端粒长度、获得性染色体不稳定、基因表达和/或皮质醇水平变化的频率。

项目成果

Familial support following childhood sexual abuse is associated with longer telomere length in adult females.

童年性虐待后的家庭支持与成年女性较长的端粒长度有关。

• DOI: 10.1007/s10865-019-00014-7
• 发表时间: 2019
• 期刊: Journal of behavioral medicine
• 影响因子: 3.1
• 作者: Sosnowski,DavidW;Kliewer,Wendy;York,TimothyP;Amstadter,AnandaB;Jackson-Cook,ColleenK;Winter,MarciaA
• 通讯作者: Winter,MarciaA