Abstract
Sleep is an essential state of decreased activity and alertness but molecular factors regulating sleep duration remain unknown. Through genome-wide association analysis in 446,118 adults of European ancestry from the UK Biobank, we identify 78 loci for self-reported habitual sleep duration (p < 5 × 10−8; 43 loci at p < 6 × 10−9). Replication is observed for PAX8, VRK2, and FBXL12/UBL5/PIN1 loci in the CHARGE study (n = 47,180; p < 6.3 × 10−4), and 55 signals show sign-concordant effects. The 78 loci further associate with accelerometer-derived sleep duration, daytime inactivity, sleep efficiency and number of sleep bouts in secondary analysis (n = 85,499). Loci are enriched for pathways including striatum and subpallium development, mechanosensory response, dopamine binding, synaptic neurotransmission and plasticity, among others. Genetic correlation indicates shared links with anthropometric, cognitive, metabolic, and psychiatric traits and two-sample Mendelian randomization highlights a bidirectional causal link with schizophrenia. This work provides insights into the genetic basis for inter-individual variation in sleep duration implicating multiple biological pathways.
Highlights
Sleep is an essential state of decreased activity and alertness but molecular factors regulating sleep duration remain unknown
This study expands our understanding of the genetic architecture of self-reported sleep duration, estimating single-nucleotide polymorphism (SNP)-based heritability at 9.8%, consistent with earlier reports[41]
We identified 76 independent loci beyond the two previously known loci (PAX8 and VRK214,17,18)
Summary
Sleep is an essential state of decreased activity and alertness but molecular factors regulating sleep duration remain unknown. Through genome-wide association analysis in 446,118 adults of European ancestry from the UK Biobank, we identify 78 loci for self-reported habitual sleep duration (p < 5 × 10−8; 43 loci at p < 6 × 10−9). Sleep is an essential homeostatically regulated state of decreased activity and alertness conserved across animal species, and both short and long sleep duration associate with chronic disease and all-cause mortality[1,2]. We extend GWAS of self-reported sleep duration in UK Biobank, test for consistency of effects in independent studies of adults and children/adolescents, determine their impact on accelerometer-derived estimates, perform pathway and tissue enrichment to highlight relevant biological processes, and explore causal relationships with disease traits
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