Identifying causal pathways between objective and subjective experiences and health outcomes: a genetically informed approach

确定客观和主观经历与健康结果之间的因果关系：基于遗传的方法

• 批准号: 2251462
• 金额: --
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2251462
• 关键词: Identifying; causal; pathways; between; objective

How an individual perceives their experiences has emerged as a potential contributing factor to physical and psychological problems. There is a growing body of evidence that indicates that objective versus subjective experiences may differentially impact health outcomes. In adolescence, there is research to support that an individual's perception of environmental exposures such as the level of neighbourhood violence, childhood maltreatment, and bullying victimization, is associated with psychological distress and poorer social mobility, over and above objective measures of the same experiences. In contrast, objective measures were not associated with poor mental health in the absence of subjective self-reports. However, it is not known the extent to which these associations between perceived experience and psychopathology reflect confounding by genetic or environmental factors (e.g., heritable individual vulnerabilities to psychopathology, or adverse family environments). As such, it is unclear whether perceived versus objective experiences are causally related to poor health outcomes. Aims and objectives This PhD will aim to examine the relationship between objective and subjective experiences with psychopathology and other physical health outcomes. A genetically informed approach will be used to test the role of genetic and environmental confounding in these associations and strengthen causal inference. The objectives are as follows: Objective 1: Carry out a systematic review and meta-analysis to test the independent associations between objective versus subjective environmental exposures with psychopathology, from childhood through to early adulthood. Objective 2: To determine the extent to which genetic mechanisms predict perceptions of environmental experiences. To do this, we intend to use polygenic scores for Body Mass Index (BMI) and relevant psychiatric traits (such as depressive disorder) and determine how they relate to the objective measure (BMI) and a corresponding perception measure (self/body-image).Objective 3: Determine the impact of objective vs subjective experiences of environmental exposure (i.e., neighbourhood adversity) on both mental health and physical health in a MZ twin difference design. Timeline of PhD Year 1: undertake training in systematic review and meta-analysis, register on PROSPERO, perform systematic review and meta-analysis for objective 1, write up for publication, upgrade to PhD from MPhil at 12 months (September 2021). Year 2: undertake training in genetic epidemiology, conduct polygenic score analyses for objective 2, write up study for publication. Year 3: Conduct analyses for objective 3, write up study for publication, present at international conferences, PhD thesis write-up and submission. Methodological considerations To achieve the objectives of this PhD, large datasets will be used (i.e. Twins Early Development Study (TEDS), the Avon Longitudinal Study of Parents and Children (ALSPAC), Child and Adolescent Twin Study in Sweden (CATSS), Millennium Cohort Study (MCS)) that feature both objective and subjective measurements of the exposures of interest (body image, neighbourhood deprivation level, stress, socioeconomic status, bullying victimization), as well as health outcomes associated (psychological and physiological measures). Supervisors will help to navigate data access and management of datasets. The PhD will involve meta-analysis and genetically informative analyses such as twin difference analyses and polygenic scoring. Implications Findings will provide insight into the causal contribution of objective vs subjective appraisal of experiences on health outcomes. This could help inform clinical practice, as causal effects of perceived environments would indicate that therapeutic approaches should address perceptions of adverse experiences to reduce risk of poor health.

一个人如何看待他们的经历已经成为身体和心理问题的一个潜在因素。有越来越多的证据表明，客观与主观经验可能会对健康结果产生不同的影响。在青少年时期，有研究表明，一个人对环境暴露的看法，如邻里暴力、童年虐待和欺凌受害的程度，与心理困扰和社会流动性较差有关，超过了对同样经历的客观衡量标准。相比之下，在没有主观自我报告的情况下，客观措施与心理健康状况不佳无关。然而，目前尚不清楚感知体验和精神病理学之间的这些关联在多大程度上反映了遗传或环境因素（例如，遗传性的个人对精神病理学的脆弱性或不利的家庭环境）。因此，目前尚不清楚感知与客观经验是否与不良健康结果有因果关系。 目的和目标这个博士将旨在研究客观和主观经验与精神病理学和其他身体健康结果之间的关系。一个遗传知情的方法将被用来测试在这些协会的遗传和环境混杂的作用，并加强因果推理。目标如下：目标一：进行系统回顾和荟萃分析，以测试从童年到成年早期客观与主观环境暴露与精神病理学之间的独立关联。目的2：确定遗传机制在多大程度上预测环境经验的看法。为此，我们打算使用身体质量指数（BMI）和相关精神病学特征（如抑郁症）的多基因评分，并确定它们如何与客观测量（BMI）和相应的感知测量（自我/身体形象）相关。在MZ双生差异设计中，邻里逆境）对心理健康和身体健康的影响。 博士一年级时间轴：进行系统性综述和荟萃分析培训，在PROSPERO上注册，为目标1进行系统性综述和荟萃分析，撰写出版物，在12个月（2021年9月）从哲学硕士升级为博士。第二年：接受遗传流行病学培训，为目标2进行多基因评分分析，撰写研究报告供出版。第3年：对目标3进行分析，撰写研究报告供出版，出席国际会议，撰写博士论文并提交。 为了实现这个博士学位的目标，将使用大型数据集（即双胞胎早期发育研究（TEDS）、雅芳父母和儿童纵向研究（ALSPAC）、瑞典儿童和青少年双胞胎研究（CATSS）、千年队列研究（MCS）），其特点是对感兴趣的暴露进行客观和主观测量（身体形象，邻里剥夺水平，压力，社会经济地位，欺凌受害），以及相关的健康结果（心理和生理措施）。主管将帮助指导数据访问和数据集管理。博士学位将涉及荟萃分析和遗传信息分析，如双胞胎差异分析和多基因评分。 影响-结果将提供深入了解的因果关系的贡献，客观与主观评价的经验对健康的结果。这可能有助于为临床实践提供信息，因为感知环境的因果效应表明，治疗方法应解决对不良经历的感知，以减少健康状况不佳的风险。