Elsevier

Sleep Medicine Reviews

Volume 17, Issue 1, February 2013, Pages 29-40
Sleep Medicine Reviews

Clinical Review
Quantitative genetic research on sleep: A review of normal sleep, sleep disturbances and associated emotional, behavioural, and health-related difficulties

https://doi.org/10.1016/j.smrv.2012.01.008Get rights and content

Summary

Over the past 50 years, well over 100 twin studies have focussed on understanding factors contributing to variability in normal sleep–wake characteristics and sleep disturbances. Whilst we have gained a great deal from these studies, there is still much to be learnt. Twin studies can be used in multiple ways to answer questions beyond simply estimating heritability. This paper provides a comprehensive review of some of the most important findings from twin studies relating to sleep to date, with a focus on studies investigating genetic and environmental influences contributing to i) objective and subjective measures of normal sleep characteristics (e.g., sleep stage organisation, sleep quality); as well as sleep disturbances and disorders such as dyssomnias (e.g., insomnia, narcolepsy) and parasomnias (e.g., sleepwalking, bruxism); ii) the persistence of sleep problems from childhood to adulthood, and the possibility that the aetiological influences on sleep change with age; iii) the associations between sleep disturbances, emotional, behavioural and health-related problems; and iv) processes of gene-environment correlation and interaction. We highlight avenues for further research, emphasising the need to further consider the aetiology of longitudinal associations between sleep disturbances and psychopathology; the genetic and environmental overlap between sleep and numerous phenotypes; and processes of gene-environment interplay and epigenetics.

Introduction

Glossary of terms

Additive genetic influence, the “adding up” of genes to influence behaviour

Aetiological influences, genetic and environmental influences underlying a phenotype/disease

Aetiology, the causes of a phenotype/disease

Broad-sense heritability, the sum of all genetic effects – additive and dominant

Dizygotic twins, non-identical twins

Dominance genetic influence, the “interaction” of genes at a particular locus which influence behaviour

Monozygotic twins, identical twins

Narrow-sense heritability, sum of all additive genetic influences

Nonshared environmental influence, environmental factors unique to each family member which account for their dissimilarity

Nosology, the classification of diseases

Quantitative genetics, the branch of behavioural genetics focussed on understanding the aetiology of numerous phenotypes using statistical methods and a special study design – e.g., family studies or twin studies

Shared environmental influence, family-wide environmental influences which act to make family members similar

There is wide inter-individual variability in sleep – in terms of both normal sleep characteristics such as sleep stage organisation, sleep timing and sleep quality; and sleep disorders such as insomnia, narcolepsy and circadian rhythm sleep disorders, to name a few.1 The diagnostic and statistical manual for mental disorders IV (DSM-IV)2 and the international classification of sleep disorders (2nd edition) (ICSD-2)3 together describe numerous sleep disorders prevalent in the general population. It is likely that this variation in sleep between individuals is accounted for by a host of genetic and environmental factors. One method for investigating the extent to which variation in a trait (phenotype) is accounted for by genetic and environmental factors is to conduct research using twins. Twin studies allow us to estimate the relative proportion of genetic and environmental influences accounting for the variation in a trait in the population. In the field of sleep research there are an abundance of twin studies investigating the aetiology of a multitude of sleep phenotypes. Investigation of the contribution of genes and environments to both normal sleep phenotypes as well as clinically diagnosable sleep disorders informs us about the possible mechanisms involved in their occurrence, and has the potential to inform the development of treatment programmes for sleep disorders. Knowledge of the aetiology of sleep phenotypes also has the potential to inform nosology (the classification of disease).

The purpose of this review is to provide an overview of some of the most important findings from twin studies in relation to sleep. The review begins by describing the twin method and illustrates how twin studies go beyond simply estimating heritability. Second, it addresses questions which have been raised by twin studies investigating variation in sleep characteristics in the normal range, as well as clinically diagnosable sleep disorders in childhood and adulthood. Third, it addresses the stability of the aetiological influences of sleep phenotypes during development, and fourth, the possible comorbidity between sleep disturbances, emotional, behavioural and health-related problems. Fifth, it considers processes of gene-environment interplay, including gene-environment correlation (rGE) and interaction (GxE). rGE is found when genetic effects influence exposure to specific environments (e.g., genetic influence on the tendency to consume caffeine). GxE refers to genotype dependent sensitivity to high risk environments (e.g., genetic influences on a trait vary as a function of some measured environmental stressor). Sixth, key findings from areas of research other than quantitative genetics are presented which have informed us about specific genetic and environmental influences on sleep; and finally avenues for future research into the aetiology of sleep are suggested.

Section snippets

The twin method

Twin studies can be used to make assumptions about the aetiology of a trait by comparing identical (monozygotic: MZ) twin pairs who share 100% of their genetic make-up, and non-identical (dizygotic: DZ) twin pairs who share on average half of their segregating genes, on a particular trait of interest (for example sleep quality measured separately in each twin). Using this method it is possible to estimate the relative proportion of three sources of variance: additive genetic influences (A, the

Results from studies using objective methods

The topography of the sleep electroencephalogram (EEG) varies between individuals.7 Studies which examine patterns of brain activity during sleep typically use polysomnography (PSG) to assess indices of sleep architecture such as sleep stage organisation, the EEG power spectra of sleep, as well as variables related to the timing, latency, length, and efficiency of sleep. Zung and Wilson performed one of the first twin studies investigating sleep using EEG in a small group of MZ twins.8 The

Aetiology of sleep difficulties and primary sleep disorders

Sleep problems are common in children, adolescents and adults.34, 35 The accumulating evidence that the magnitude of genetic and environmental factors on numerous phenotypes varies across the life-span (e.g., see4) highlights the importance of considering age-dependent effects in relation to sleep problems. In this section we present important findings from quantitative genetic research in relation to sleep difficulties and primary sleep disorders in childhood and adulthood separately.

Co-occurrence and comorbidity

In addition to the co-occurrence of similar types of sleep disorders, certain sleep problems are known to co-occur with emotional, behavioural and health-related problems. Finding that sleep difficulties are comorbid with other disorders may be useful in identifying individuals at risk for such disorders. Several twin studies have assessed the comorbidity between sleep and other phenotypes in children and adults, as outlined below.

Specifying genes and environments

Although the classical twin design does not typically provide information as to which genes or which environmental influences may be contributing to a particular phenotype, twin studies can be used to guide molecular geneticists and epidemiologists as to where to focus their search for specific factors. Identifying specific genes/environments may help to highlight those at risk of sleep difficulties and aid in reducing or ameliorating these symptoms in genetically vulnerable individuals. One

Gene-environment interplay

Although genetic and environmental influences may work independently, research is beginning to acknowledge that these factors work in concert to influence behaviour via processes such as gene-environment correlation and interaction. In the molecular genetic field this work has been highly influential with regards to a range of traits such as depression and anxiety,107, 108 yet research assessing the interplay between genetic and environmental influences focussed on sleep is scarce. One

Conclusions and future directions

As is evident, twin studies allow us to tackle challenging questions regarding the ways in which genetic and environmental influences affect behaviour. Exploiting these techniques has led to new discoveries in the field of sleep research which has advanced our understanding of the factors underlying the physiological processes of sleep, as well as factors implicated in chronic sleep disorders in children and adults. There are numerous on going large-scale twin studies worldwide and research

Conflict of interest

The authors declare no conflict of interest.

Acknowledgements

During this work Alice M. Gregory was supported by a Leverhulme Trust Fellowship.

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