title: A K(ATP) channel gene effect on sleep duration: from genome-wide association studies to function in Drosophila.
abstract: 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.
authors: Institute of Medical Psychology, Ludwig-Maximilians-University, Munich, Germany.
authors: K V
authors: KV
authors: Allebrandt
authors: N
authors: N
authors: Amin
authors: B
authors: B
authors: Müller-Myhsok
authors: T
authors: T
authors: Esko
authors: M
authors: M
authors: Teder-Laving
authors: R V D M
authors: RV
authors: Azevedo
authors: C
authors: C
authors: Hayward
authors: J
authors: J
authors: van Mill
authors: N
authors: N
authors: Vogelzangs
authors: E W
authors: EW
authors: Green
authors: S A
authors: SA
authors: Melville
authors: P
authors: P
authors: Lichtner
authors: H-E
authors: HE
authors: Wichmann
authors: B A
authors: BA
authors: Oostra
authors: A C J W
authors: AC
authors: Janssens
authors: H
authors: H
authors: Campbell
authors: J F
authors: JF
authors: Wilson
authors: A A
authors: AA
authors: Hicks
authors: P P
authors: PP
authors: Pramstaller
authors: Z
authors: Z
authors: Dogas
authors: I
authors: I
authors: Rudan
authors: M
authors: M
authors: Merrow
authors: B
authors: B
authors: Penninx
authors: C P
authors: CP
authors: Kyriacou
authors: A
authors: A
authors: Metspalu
authors: C M
authors: CM
authors: van Duijn
authors: T
authors: T
authors: Meitinger
authors: T
authors: T
authors: Roenneberg
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D030801:Animals, Genetically Modified; D015331:Cohort Studies; D004330:Drosophila / Q000235:genetics / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D051664:Kv1.3 Potassium Channel / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D017440:Photoperiod; D051191:Plakophilins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D034622:RNA Interference / Q000502:physiology; D011955:Receptors, Drug / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D012893:Sleep Wake Disorders / Q000235:genetics*; D064233:Sulfonylurea Receptors; D044465:White People; D055815:Young Adult
chemical_list: C577510:ABCC9 protein, human; D018528:ATP-Binding Cassette Transporters; D029721:Drosophila Proteins; C097044:KCNAB1 protein, human; D051664:Kv1.3 Potassium Channel; C495337:PKP2 protein, human; D051191:Plakophilins; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D012097:Repressor Proteins; D064233:Sulfonylurea Receptors; C115159:pan protein, Drosophila