Genetic associations between cognitive ability, negative emotions, and mental and physical health

Abstract

Human population-based studies have shown that cognitive ability and negative emotions are associated with later health outcomes. Part of this association might be due to shared genetic influences. The present thesis has two main objectives. The first is to examine the shared genetic aetiology between cognitive ability and mental and physical health. The second is to examine the shared genetic aetiology between the tendency to experience negative emotions and mental and physical health. Chapter 1 and Chapter 2 provide an introductory overview of the field of individual differences in psychology, with the first Chapter focussing on cognitive ability and the second on personality (especially neuroticism). Each of these Chapters provide an historical overview of the two traits, followed by the associations with health outcomes, and finish by exploring the genetic aetiology of both cognitive ability and negative emotions and the potential genetic overlap with health outcomes. Chapter 3 focusses on the main cohort analysed in this thesis, the UK Biobank. This Chapter outlines the study population and its demographics, and provides a detailed account of the main variables examined in this thesis. Chapters 4 to 7 present the empirical work and are split in two parts; the first part (Chapters 4 and 5), focusses on cognitive ability. The second part (Chapters 6 and 7) focusses on negative emotions. Chapter 4 presents two studies, examining the shared genetic aetiology between cognitive ability and mental and physical health using linkage disequilibrium score regression and polygenic profile analysis; Mendelian Randomization is used to test for direction of effect between cognitive ability and physical health. The results indicate a substantially shared genetic aetiology between cognitive ability and both physical and mental health. No evidence was found for a causal association between cognitive ability and physical health. Chapter 5 examines the genetic aetiology of a test of executive cognitive function, the Trail- Making test, which has been closely associated with other cognitive abilities. This Chapter also examines the shared genetic aetiology between the Trail-Making test, general cognitive ability, processing speed, and memory, using a range of molecular genetic techniques. The results provide heritability estimates ranging from 7% to 22% for the different Trail-Making test measures, and there are new genetic associations with the Trail-Making test. A considerable degree of genetic overlap is found between the Trail-Making test and general cognitive function and processing speed in particular. Chapter 6 explores the shared genetic aetiology between the personality trait of neuroticism and mental and physical health using Linkage Disequilibrium Score Regression and polygenic profile analysis. The results show significant genetic correlations between neuroticism and major depressive disorder, schizophrenia, and anorexia. Polygenic profile scores for multiple mental health traits, as well as body mass index, coronary artery disease, and smoking status are predictive of neuroticism. Chapter 7 examines the genetic contributions to self-reported tiredness, a trait strongly related to the tendency to experience negative emotions; it also examines the genetic overlap with health outcomes using Linkage Disequilibrium Score Regression and polygenic profile analysis. The results demonstrate a significant heritability estimate of 8% for self-reported tiredness. Extensive genetic overlap is identified between self-reported tiredness and mental and physical health, and particularly with the trait of neuroticism. Finally, Chapter 8 summarizes the empirical findings presented in Chapters 4 to 7. This Chapter discusses limitations of the methods used in this thesis, and offers suggestions for future research in the field of genetic epidemiology, especially as applied to health and psychological differences.