A K(ATP) channel gene effect on sleep duration: from genome-wide association studies to function in Drosophila.
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Allebrandt KV, Amin N, Muller-Myhsok B, Esko T, Teder-Laving M, Azevedo RV, Hayward C, van Mill J, Vogelzangs N, Green EW, Melville SA, Lichtner P, Wichmann HE, Oostra BA, Janssens AC, Campbell H, Wilson JF, Hicks AA, Pramstaller PP, Dogas Z, Rudan I, Merrow M, Penninx B, Kyriacou CP, Metspalu A, van Duijn CM, Meitinger T, Roenneberg T
A K(ATP) channel gene effect on sleep duration: from genome-wide association studies to function in Drosophila.
Mol Psychiatry. 2013 Jan;18(1):122-32. doi: 10.1038/mp.2011.142. Epub 2011 Nov 22.
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- 22105623 [ View in PubMed]
- 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 x 10(-8)) in the ABCC9 gene that explains approximately 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.