Epigenetics: Environment, Embodiment and Equality (E4)

人们普遍认为，早期生活的影响塑造了我们整个生命过程中的发育、健康和行为结果。表观遗传机制越来越多地牵涉到这些复杂的相互作用中，并为理解(I)我们的环境的哪些方面影响基因调控，(Ii)我们的环境和生活方式如何体现在人类生物学中，在什么时间框架内和以何种程度持续存在，以及(Iii)社会和生物不平等如何影响发展和健康提供了关键。我们将利用雅芳父母和儿童纵向研究(目前拥有世界上所有出生队列研究中最广泛的纵向表观遗传学数据收集)作为解决这些概念的平台，并通过与其他七个队列研究的合作，将我们的调查扩展到整个生命过程，以了解早期生活中不同的社会和环境经验如何影响表观遗传签名和下游结果。我们将通过实施因果分析方法来扩展这些分析，包括孟德尔随机化的新应用，以加强我们观察到的关联中的因果推断。此外，我们将应用社会结构/理论来阐述这些解释。分析表观遗传过程在整个生命过程中将环境与发展和健康联系起来的作用需要产生、分析和解释复杂数据的能力。表观遗传学数据的高维、动态特征要求生物信息学和统计方法方面的高级能力。近年来，我们在生成表观遗传学数据、发展和完善信息学和统计技能方面投入了大量精力，并通过这个项目提出将它们应用于上述问题。拟议的工作将扩大当前的研究活动，汇集社会和生物科学家的技能，将最近开发的方法应用于表观遗传学和社会科学交界处尚未解决的问题。项目活动的一个主要组成部分将是促进跨学科合作、培训机会以及广泛传播方法和科学成果。我们将利用我们的合作研究团队在生物信息学、计算科学、计量经济学、教育学、表观遗传学、生命过程流行病学、心理学、数量遗传学、社会科学和统计学方面的专业知识来执行拟议的项目。

It is widely accepted that early life influences shape our development and health and behavioural outcomes across the life course. Epigenetic mechanisms are increasingly implicated in these complex interactions and provide a key to understanding (i) what aspects of our environment impact upon gene regulation, (ii) how our environment and way of living become embodied in human biology, over what timeframe and with what degree of persistence and (iii) how social and biological inequality may influence development and health.This project builds upon a substantial foundation of epigenetic research in richly characterised longitudinal cohort studies to explore these concepts of environment, embodiment and inequality. We will utilise the Avon Longitudinal Study of Parents and Children, which currently has the most extensive collection of longitudinal epigenetic data of any birth cohort study in the world, as a platform to address these concepts and through collaboration with seven other cohorts we will extend our investigations across the entire lifecourse to understand how different social and environmental experiences in early life operate to influence epigenetic signatures and downstream outcomes. We will extend these analyses by implementing causal analysis methods, including novel applications of Mendelian randomization, to strengthen causal inference in the associations we observe. Further, we will apply social constructs/theories to elaborate these interpretations.Analysis of the role of epigenetic processes in linking the environment with development and health across the lifecourse requires the capacity to generate, analyse and interpret complex data. The high dimensional, dynamic characteristics of epigenetic data require advanced competencies in bioinformatics and statistical methods. We have invested considerable effort in generating epigenetic data, developing and refining informatics and statistical skills over recent years and through this project propose to apply them to the questions outlined above.The proposed work will extend current research activities, drawing together skills of social and biological scientists to apply recently developed methodologies to unresolved issues at the interface of epigenetics and social science. A major component of project activities will be the promotion of inter-disciplinary collaboration, training opportunities and widespread dissemination of both methods and scientific outputs. We will draw upon the expertise of our co-investigator team in bioinformatics, computational science, econometrics, education, epigenetics, lifecourse epidemiology, psychology, quantitative genetics, social science and statistics to execute the proposed project.