Exploring the aetiology of psychological distress and its associations with physical health and health-related quality of life

Student thesis: Doctoral ThesisDoctor of Philosophy


Mental and physical health often co-occur, and this comorbidity can negatively impact quality of life. Twin studies suggest heritability of measures of psychological distress, including anxiety and depression, as well as physical health markers such as cardiovascular health. Yet, there is still limited behaviour genetic and epigenetic work in understanding how these two domains are related, as well as lack of representation in non-western populations.

The first empirical project involves investigating the genetic and environmental architecture of anxiety symptoms in a Dutch twin sample (Twins Interdisciplinary Neuroticism Study; TWINS) and exploring its associations with three indicators of cardiac autonomic functioning: inter-beat interval, heart rate variability and baroreflex sensitivity. This multivariate twin project adds to much needed behaviour genetics research on the relationships between anxiety and cardiovascular health and is now published as a research paper in Twin Research & Human Genetics (Nas, Riese, van Roon & Rijsdijk, 2020).

The second research project involves bivariate twin analyses between anxiety symptoms and health-related quality of life in a Sri-Lankan twin and singleton population (Colombo Twin and Singleton study; CoTASS). This project explores both the aetiology of these traits, as well as providing insight into their covariance, via phenotypic, genetic, and environmental correlations. This project is published as a research paper in Behaviour Genetics (Nas et al, 2021). This CoTASS dataset was also used in my third project, which seeks to answer remaining questions regarding causality between psychological distress and physical wellbeing. Using the direction-of-causation (DOC) twin model, I show a potential causal direction suggesting that poor mental health may be a precursor to decline in physical health. The paper stemming from this project is currently under review in the Journal of Affective Disorders Reports.

The fourth component of this thesis involves investigating the epigenetic nature of psychological distress. Although there has been a growing literature surrounding DNA methylation and its involvement in psychiatric conditions, there is relatively little known about the role of global DNA methylation. In this project, we explore the relationships between global DNA methylation (quantified through the repetitive marker, LINE-1 in DNA) & severity of psychological distress using twin datasets from ongoing studies (Social Relationships Study; SRS & Twins’ Early development Study; TEDS). In addition, we make use of the twin nature of the datasets to conduct within-twin analyses to investigate the role of epigenetic profiles in psychological distress. In the final chapter I discuss these findings, in light of possible limitations as well as possible future directions.
Date of Award1 May 2022
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorChloe Wong (Supervisor) & Fruhling Rijsdijk (Supervisor)

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