Genetic and Environmental Influences on Sleep Quality: Quantitative and Molecular Genetic Approaches to an Understanding of Individual Differences

There are vast inter-individual differences in sleep quality in the general population – whilst some individuals sleep well with little or no sleep disturbance, others experience frequent sleep disturbances, problems which often manifest into chronic sleep disorders such as insomnia. The aim of this thesis is to explore factors accounting for these observed differences in sleep quality between individuals. Using data from a large-scale twin study this thesis uses behavioural genetic techniques to investigate genetic and environmental influences on sleep quality in a sample of 1,556 twins and siblings aged 18-27 years. The first four studies use quantitative genetic techniques to investigate 1) associations between components of sleep quality and the overlap in the genetic and environmental influences accounting for them; 2) specific non-shared environmental influences on global sleep quality; 3) the presence of gene-environment interplay between sleep quality and dependent negative life events; and 4) the association between sleep quality and diurnal preference, and the overlap in their aetiological influences. Most importantly, there was substantial genetic overlap between individual components of sleep quality (rA mostly ≥.50); sleep quality and diurnal preference (rD = .52[95% CI=.37-.70]); and sleep quality and dependent negative life events (rD = .63[.45-.83]) – the latter finding providing evidence of gene-environment correlation. In general, non-shared environmental overlap was small (rE mostly ≤.40). The final study used a candidate gene approach to investigate associations between sleep quality and diurnal preference with 5HTTLPR, PER3, and CLOCK 3111 – polymorphisms hypothesized to be implicated in sleep and/or the circadian system. An association was found between the ‘long’ allele of 5HTTLPR and poor sleep quality (β = -.34, p<.01). This thesis utilises the twin method in novel ways in the context of sleep research and advances knowledge of the genetic and environmental underpinnings of the variation in sleep quality in healthy young adults

Genetic and environmental influences on sleep quality : quantitative and molecular genetic approaches to an understanding of individual differences

There are vast inter-individual differences in sleep quality in the general population – whilst some individuals sleep well with little or no sleep disturbance, others experience frequent sleep disturbances, problems which often manifest into chronic sleep disorders such as insomnia. The aim of this thesis is to explore factors accounting for these observed differences in sleep quality between individuals. Using data from a large-scale twin study this thesis uses behavioural genetic techniques to investigate genetic and environmental influences on sleep quality in a sample of 1,556 twins and siblings aged 18-27 years. The first four studies use quantitative genetic techniques to investigate 1) associations between components of sleep quality and the overlap in the genetic and environmental influences accounting for them; 2) specific non-shared environmental influences on global sleep quality; 3) the presence of gene-environment interplay between sleep quality and dependent negative life events; and 4) the association between sleep quality and diurnal preference, and the overlap in their aetiological influences. Most importantly, there was substantial genetic overlap between individual components of sleep quality (rA mostly ≥.50); sleep quality and diurnal preference (rD = .52[95% CI=.37-.70]); and sleep quality and dependent negative life events (rD = .63[.45-.83]) – the latter finding providing evidence of gene-environment correlation. In general, non-shared environmental overlap was small (rE mostly ≤.40). The final study used a candidate gene approach to investigate associations between sleep quality and diurnal preference with 5HTTLPR, PER3, and CLOCK 3111 – polymorphisms hypothesized to be implicated in sleep and/or the circadian system. An association was found between the ‘long’ allele of 5HTTLPR and poor sleep quality (β = -.34, p<.01). This thesis utilises the twin method in novel ways in the context of sleep research and advances knowledge of the genetic and environmental underpinnings of the variation in sleep quality in healthy young adults.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Anxiety mediates the relationship between perfectionism and insomnia symptoms: A longitudinal study

Objectives Individuals with insomnia often report aspects of perfectionism and symptoms of anxiety and depression. Investigation of these factors together has been limited. As such, the aim of the present study was to examine the extent to which the association between perfectionism and insomnia symptoms was mediated by anxiety and depression, concurrently and longitudinally. Methods Seventy-six members from the general-population participated at baseline. Data from 57 participants were subsequently analysed at twelve-month follow-up. Insomnia symptoms were assessed using The Insomnia Severity Index (ISI). Perfectionism was assessed using two Multidimensional Perfectionism Scales (F-MPS; HF-MPS). Symptoms of anxiety and depression were assessed using The Hospital Anxiety and Depression Scale (HADS). Correlational analysis examined longitudinal associations between perfectionism and insomnia symptoms. Hierarchical regression analysis examined whether significant associations remained after controlling for anxiety and depression. Results Baseline insomnia symptoms were associated with future doubts about action. Further, this relationship was mediated by preceding symptoms of anxiety and concurrent symptoms of insomnia. Similarly, baseline insomnia symptoms were also associated with future parental criticism. However this relationship was partially mediated by preceding symptoms of anxiety, and was not mediated by concurrent insomnia symptoms. Conclusions Symptoms of insomnia appear to be related to an increase in negative perfectionistic thinking in the form of doubts about action and parental criticism, however these relationships appear to be mediated by symptoms of anxiety. Therefore, treatments for insomnia should address anxiety symptoms with the prospect of preventing the accentuation of aspects of perfectionism due to poor sleep

Polymorphisms in the circadian expressed genes PER3 and ARNTL2 are associated with diurnal preference and GNβ3 with sleep measures

Sleep and circadian rhythms are intrinsically linked, with several sleep traits, including sleep timing and duration, influenced by both sleep homeostasis and the circadian phase. Genetic variation in several circadian genes has been associated with diurnal preference (preference in timing of sleep), although there has been limited research on whether they are associated with other sleep measurements. We investigated whether these genetic variations were associated with diurnal preference (Morningness-Eveningness Questionnaire) and various sleep measures, including: the global Pittsburgh Sleep Quality index score; sleep duration; and sleep latency and sleep quality. We genotyped 10 polymorphisms in genes with circadian expression in participants from the G1219 sample (n = 966), a British longitudinal population sample of young adults. We conducted linear regressions using dominant, additive and recessive models of inheritance to test for associations between these polymorphisms and the sleep measures. We found a significant association between diurnal preference and a polymorphism in period homologue 3 (PER3) (P < 0.005, recessive model) and a novel nominally significant association between diurnal preference and a polymorphism in aryl hydrocarbon receptor nuclear translocator-like 2 (ARNTL2) (P < 0.05, additive model). We found that a polymorphism in guanine nucleotide binding protein beta 3 (GNβ3) was associated significantly with global sleep quality (P < 0.005, recessive model), and that a rare polymorphism in period homologue 2 (PER2) was associated significantly with both sleep duration and quality (P < 0.0005, recessive model). These findings suggest that genes with circadian expression may play a role in regulating both the circadian clock and sleep homeostasis, and highlight the importance of further studies aimed at dissecting the specific roles that circadian genes play in these two interrelated but unique behaviours

Longitudinal stability of genetic and environmental influences on the association between diurnal preference and sleep quality in young adult twins and siblings

Overlapping genetic influences have been implicated in diurnal preference and subjective sleep quality. Our overall aim was to examine overlapping concurrent and longitudinal genetic and environmental effects on diurnal preference and sleep quality over ~5 years. Behavioural genetic analyses were performed on data from the longitudinal British G1219 study of young adult twins and non-twin siblings. 1556 twins and siblings provided data on diurnal preference (Morningness-Eveningness Questionnaire) and sleep quality (Pittsburgh Sleep Quality Index) at time 1 (mean age=20.30 years, SD=1.76; 62% female); and 862 participated at time 2 (mean age=25.30 years, SD=1.81; 66% female). Preference for eveningness was associated with poorer sleep quality at both time-points (r=.25[95% confidence intervals, (CI)=.20-.30], and r=.21[CI=.15-.28]). There was substantial overlap in the genetic influences on diurnal preference and sleep quality individually, across time (genetic correlations [rA’s]: .64[95% CI = .59-.67] and .48[95% CI = .42-.53]). There were moderate genetic correlations between diurnal preference and sleep quality concurrently and longitudinally (rAs=.29-.60). Non-shared environmental overlap was substantially smaller for all cross-phenotype associations (non-shared environmental correlations [rE’s]=-.02-.08). All concurrent and longitudinal associations within and between phenotypes were largely accounted for by genetic factors (explaining between 60%-100% of the associations). All shared environmental effects were non-significant. Non-shared environmental influences played a smaller role on the associations between phenotypes (explaining between -.06%-40% of the associations). These results suggest that to some extent similar genes contribute to the stability of diurnal preference and sleep quality throughout young adulthood, but also that different genes play a part over this relatively short time-frame. While there was evidence of genetic overlap between phenotypes concurrently and longitudinally, the possible emergence of new genetic factors (or decline of previously associated factors) suggests that molecular genetic studies focussing on young adults should consider more tightly specified age-groups, given that genetic effects may be time-specific

Anxiety mediates the relationship between multidimensional perfectionism and insomnia disorder

Individuals with insomnia often report aspects of perfectionism alongside symptoms of anxiety and depression. However, there has been limited examination of these factors together. The current study investigated whether individuals with insomnia report increased perfectionism compared to normal-sleepers. Further, the mediating role of anxiety and depression was examined. Participants were 39 individuals with DSM-5 defined Insomnia Disorder, and 39 normal-sleepers, who completed two measures of multidimensional perfectionism and the Hospital Anxiety and Depression Scale. Results demonstrated that, compared to normal-sleepers, individuals with insomnia display increased perfectionistic traits of: concern over mistakes, doubts about action, and parental criticism. In addition, these differences were partiality mediated by symptoms of anxiety, but not depression. Our findings highlight the significance of treating symptoms of anxiety with the prospect of alleviating negative thoughts concerning one's mistakes, doubts about action, and perception of parental criticism, which may contribute to insomnia

Sleep-related attentional bias for tired faces in insomnia: evidence from a dot-probe paradigm

People with insomnia often display an attentional bias for sleep-specific stimuli. However, prior studies have mostly utilized sleep-related words and images, and research is yet to examine whether people with insomnia display an attentional bias for sleep-specific (i.e. tired appearing) facial stimuli. This study aimed to examine whether individuals with insomnia present an attentional bias for sleep-specific faces depicting tiredness compared to normal-sleepers. Additionally, we aimed to determine whether the presence of an attentional bias was characterized by vigilance or disengagement. Forty-one individuals who meet the DSM-5 criteria for Insomnia Disorder and 41 normal-sleepers completed a dot-probe task comprising of neutral and sleep-specific tired faces. The results demonstrated that vigilance and disengagement scores differed significantly between the insomnia and normal-sleeper groups. Specifically, individuals with insomnia displayed difficulty in both orienting to and disengaging attention from tired faces compared to normal-sleepers. Using tired facial stimuli, the current study provides novel evidence that insomnia is characterized by a sleep-related attentional bias. These outcomes support cognitive models of insomnia by suggesting that individuals with insomnia monitor tiredness in their social environment

The Genesis 12–19 (G1219) Study: A Twin and Sibling Study of Gene–Environment Interplay and Adolescent Development in the UK

The Genesis 12–19 (G1219) Study is an ongoing longitudinal study of a sample of UK twin pairs, non-twin sibling pairs, and their parents. G1219 was initially designed to examine the role of gene–environment interplay in adolescent depression. However, since then data have continued to be collected from both parents and their offspring into young adulthood. This has allowed for longitudinal analyses of depression and has enabled researchers to investigate multiple phenotypes and to ask questions about intermediate mechanisms. The study has primarily focused on emotional development, particularly depression and anxiety, which have been assessed at multiple levels of analysis (symptoms, cognitions, and relevant environmental experiences). G1219 has also included assessment of a broader range of psychological phenotypes ranging from antisocial behaviors and substance use to sleep difficulties, in addition to multiple aspects of the environment. DNA has also been collected. The first wave of data collection began in the year 1999 and the fifth wave of data collection will be complete before the end of 2012. In this article, we describe the sample, data collection, and measures used. We also summarize some of the key findings to date

Pre-Sleep Cognitive Arousal Is Negatively Associated with Sleep Misperception in Healthy Sleepers during Habitual Environmental Noise Exposure: An Actigraphy Study

Specific noises (e.g., traffic or wind turbines) can disrupt sleep and potentially cause a mismatch between subjective sleep and objective sleep (i.e., “sleep misperception”). Some individuals are likely to be more vulnerable than others to noise-related sleep disturbances, potentially as a result of increased pre-sleep cognitive arousal. The aim of the present study was to examine the relationships between pre-sleep cognitive arousal and sleep misperception. Sixteen healthy sleepers participated in this naturalistic, observational study. Three nights of sleep were measured using actigraphy, and each 15-s epoch was classified as sleep or wake. Bedside noise was recorded, and each 15-s segment was classified as containing noise or no noise and matched to actigraphy. Participants completed measures of habitual pre-sleep cognitive and somatic arousal and noise sensitivity. Pre-sleep cognitive and somatic arousal levels were negatively associated with subjective–objective total sleep time discrepancy (p < 0.01). There was an association between sleep/wake and noise presence/absence in the first and last 90 min of sleep (p < 0.001). These results indicate that higher levels of habitual pre-sleep arousal are associated with a greater degree of sleep misperception, and even in healthy sleepers, objective sleep is vulnerable to habitual bedside noise