Genetic Associations with Sleep Traits and Disorders

Sleep characteristics such as duration, quality, timing and disorders including insomnia and excessive daytime sleepiness are influenced by complex genetic factors. Heritability estimates from family and twin studies indicate that up to 40% of inter-individual variation in sleep traits can be attributed to inherited DNA sequence variation. Large-scale genome-wide association studies (GWAS) have identified numerous single-nucleotide polymorphisms (SNPs) linked to chronotype, sleep duration, sleep efficiency and napping propensity. Many implicated loci map to genes involved in circadian regulation, neurotransmitter signalling and neurodevelopmental pathways. Polygenic risk scores derived from these GWAS capture aggregate genetic liability and can predict susceptibility to sleep disorders and related health outcomes. Mendelian randomisation analyses have further begun to disentangle causal relationships between sleep traits and cardiometabolic, psychiatric and neurodegenerative disorders. Epigenetic studies, including DNA methylation profiling, suggest that environmental and behavioural factors may also modulate gene expression patterns in sleep-related pathways. These advances deepen understanding of molecular mechanisms governing sleep and pave the way for precision medicine approaches to intervene in sleep disorders and their comorbidities.

Research from Nature Portfolio

A genome-wide analysis of self-reported daytime napping in over 450,000 adults uncovered more than 120 loci that influence nap frequency and intensity. Cluster analysis of these loci revealed distinct biological mechanisms underpinning sleep propensity, arousal regulation and metabolic integration. Mendelian randomisation provided evidence that higher genetic predisposition to frequent napping may causally contribute to elevated blood pressure and increased central adiposity, highlighting potential cardiometabolic consequences.
In an objective assessment of sleep using wrist-worn accelerometers in approximately 85,000 individuals, investigators identified nearly 50 genetic associations across eight derived traits, including nocturnal sleep duration, sleep fragmentation and efficiency. A missense variant in a phosphodiesterase gene was pinpointed as likely causal for sleep duration variation, and loci regulating serotonin processing were enriched among sleep-quality signals. This work underscores the added value of objective measures in unravelling the genetic architecture of human sleep behaviour.

Genetic Associations with Sleep Traits and Disorders publication trend

The graph below shows the total number of articles in genetic associations with sleep traits and disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Genome-wide association study: A research approach that scans the entire genome for common genetic variants associated with a trait or disorder.

Single-nucleotide polymorphism (SNP): A single base-pair variation in genomic DNA occurring commonly within a population.

Polygenic risk score: An aggregate measure of genetic susceptibility calculated by summing risk alleles weighted by their effect sizes from GWAS.

Mendelian randomisation: A method that uses genetic variants as proxies for modifiable exposures to infer causal relationships with outcomes.

Chronotype: Individual preference for timing of sleep and wakefulness, often described as “morningness” or “eveningness.”

Epigenetics: The study of heritable changes in gene expression not caused by alterations in the DNA sequence, such as DNA methylation.

References

1. Identifying the potential causal role of insomnia symptoms on 11,409 health-related outcomes: a phenome-wide Mendelian randomisation analysis in UK Biobank. BMC Medicine (2023).
2. Shared genetic architecture and causal relationship between sleep behaviors and lifespan. Translational Psychiatry (2024).
3. Genetic studies of accelerometer-based sleep measures yield new insights into human sleep behaviour. Nature Communications (2019).
4. Genetic determinants of daytime napping and effects on cardiometabolic health. Nature Communications (2021).