A K(ATP) channel gene effect on sleep duration: from genome-wide association studies to function in Drosophila.
Mol Psychiatry
; 18(1): 122-32, 2013 Jan.
Article
in En
| MEDLINE
| ID: mdl-22105623
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sleep Wake Disorders
/
Genetic Predisposition to Disease
/
Polymorphism, Single Nucleotide
/
Kv1.3 Potassium Channel
/
Genome-Wide Association Study
Type of study:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Systematic_reviews
Limits:
Adolescent
/
Adult
/
Aged
/
Aged80
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Mol Psychiatry
Journal subject:
BIOLOGIA MOLECULAR
/
PSIQUIATRIA
Year:
2013
Type:
Article
Affiliation country:
Germany