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身体和心理问题的一个潜在的促成因素。越来越多的证据表明，客观体验和主观体验可能会对健康结果产生不同的影响。在青春期，有研究表明，个人对环境暴露的感知，如邻里暴力、童年虐待和欺凌受害者的程度，与心理痛苦和较差的社会流动性有关，超过了相同经历的客观衡量标准。相比之下，在缺乏主观自我报告的情况下，客观测量与较差的精神健康无关。然而，尚不清楚知觉经验和精神病理学之间的这些联系在多大程度上反映了遗传或环境因素(例如，精神病理学的可遗传个体脆弱性，或不利的家庭环境)的混淆。因此，目前尚不清楚感知与客观经历是否与不良健康结果之间存在因果关系。目的和目标本博士将致力于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。将使用遗传知情的方法来测试遗传和环境混淆在这些关联中的作用，并加强因果推断。目标1：开展一项系统的综述和荟萃分析，以检验从儿童期到成年期，客观和主观环境暴露与精神病理学之间的独立联系。目的2：确定遗传机制在多大程度上预测环境体验的感知。为此，我们打算使用身体质量指数(BMI)和相关精神特征(如抑郁障碍)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。目标3：在MZ双胞胎差异设计中确定客观和主观环境暴露体验(即邻里逆境)对心理健康和身体健康的影响。博士第一年的时间表：接受系统审查和荟萃分析方面的培训，在Propero上注册，为目标1进行系统审查和荟萃分析，撰写论文以供发表，在12个月内(2021年9月)从MPHil升级到博士学位。第二年：接受遗传流行病学培训，为目标2进行多基因得分分析，撰写研究报告以供发表。第三年：为目标3进行分析，撰写研究报告以供发表，出席国际会议，撰写和提交博士论文。为了实现这一博士学位的目标，将使用大数据集(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))，其特征是对感兴趣的暴露(身体形象、邻里剥夺水平、压力、社会经济状况、欺凌受害者)以及相关的健康结果(心理和生理措施)进行客观和主观测量。监督员将帮助导航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。研究结果将深入了解客观与主观评估经验对健康结果的因果贡献。这可能有助于为临床实践提供信息，因为感知环境的因果关系将表明，治疗方法应该解决不良体验的感知，以降低健康不良的风险。

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.