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

一个人如何看待他们的经历已经成为造成身体和心理问题的潜在因素。越来越多的证据表明，客观体验与主观体验可能会对健康结果产生不同的影响。在青春期，有研究支持个人对环境暴露的感知，如邻里暴力、童年虐待和欺凌受害的程度，与心理困扰和较差的社会流动性有关，超过了对相同经历的客观测量。相比之下，在没有主观自我报告的情况下，客观测量与心理健康状况不佳无关。然而，目前尚不清楚这些感知经验和精神病理之间的关联在多大程度上反映了遗传或环境因素的混杂（例如，遗传的个体对精神病理的脆弱性，或不利的家庭环境）。因此，目前尚不清楚感知体验与客观体验是否与不良健康结果有因果关系。目的和目标本博士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。一种遗传知情的方法将用于测试遗传和环境混杂在这些关联中的作用，并加强因果推理。目标1：进行系统回顾和荟萃分析，以测试从童年到成年早期，客观和主观环境暴露与精神病理之间的独立关联。目的2：确定遗传机制预测环境体验感知的程度。为了做到这一点，我们打算使用身体质量指数（BMI）和相关精神特征（如抑郁症）的多基因评分，并确定它们与客观测量（BMI）和相应的感知测量（自我/身体形象）的关系。目的3：在MZ双胞胎差异设计中确定环境暴露的客观与主观体验（即邻里逆境）对心理健康和身体健康的影响。博士一年级时间表：接受系统评价和元分析培训，在PROSPERO注册，对目标1进行系统评价和元分析，撰写论文发表，在12个月（2021年9月）时从MPhil升级为博士。第二年：进行遗传流行病学培训，对目标2进行多基因评分分析，撰写研究论文发表。第三年：对目标3进行分析，撰写研究报告发表，出席国际会议，博士论文撰写和提交。为了实现本博士的目标，将使用大型数据集（即双胞胎早期发展研究（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）），这些数据集具有客观和主观测量感兴趣的暴露（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）。主管将帮助引导数据访问和数据集管理。博士课程将涉及元分析和基因信息分析，如双胞胎差异分析和多基因评分。研究结果将深入了解对健康结果的客观与主观评价的因果关系。这有助于为临床实践提供信息，因为感知环境的因果效应将表明，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。

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.