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Humans sleep approximately a third of their lifetime. The observation that individuals with either long or short sleep duration show associations with metabolic syndrome and psychiatric disorders suggests that the length of sleep is adaptive. Although sleep duration can be influenced by photoperiod (season) and phase of entrainment (chronotype), human familial sleep disorders indicate that there is a strong genetic modulation of sleep. Therefore, we conducted high-density genome-wide association studies for sleep duration in seven European populations (N=4251). We identified an intronic variant (rs11046205; P=3.99 × 10(-8)) in the ABCC9 gene that explains ≈5% of the variation in sleep duration. An influence of season and chronotype on sleep duration was solely observed in the replication sample (N=5949). Meta-analysis of the associations found in a subgroup of the replication sample, chosen for season of entry and chronotype, together with the discovery results showed genome-wide significance. RNA interference knockdown experiments of the conserved ABCC9 homologue in Drosophila neurons renders flies sleepless during the first 3 h of the night. ABCC9 encodes an ATP-sensitive potassium channel subunit (SUR2), serving as a sensor of intracellular energy metabolism.

Original publication

DOI

10.1038/mp.2011.142

Type

Journal article

Journal

Molecular psychiatry

Publication Date

01/2013

Volume

18

Pages

122 - 132

Addresses

Institute of Medical Psychology, Ludwig-Maximilians-University, Munich, Germany.

Keywords

Myocardium, Animals, Animals, Genetically Modified, Humans, Drosophila, Genetic Predisposition to Disease, ATP-Binding Cassette Transporters, Potassium Channels, Inwardly Rectifying, Drosophila Proteins, Receptors, Drug, Repressor Proteins, Cohort Studies, RNA Interference, Genotype, Phenotype, Polymorphism, Single Nucleotide, Photoperiod, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, European Continental Ancestry Group, Female, Male, Plakophilins, Kv1.3 Potassium Channel, Genome-Wide Association Study, Young Adult, Sulfonylurea Receptors, Sleep Wake Disorders