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

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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.