A K(ATP) channel gene effect on sleep duration: from genome-wide association studies to function in Drosophila

K. V. Allebrandt, N. Amin, B. Mueller-Myhsok, T. Esko, M. Teder-Laving, R. V. D. M. Azevedo, C. Hayward, J. van Mill, N. Vogelzangs, E. W. Green, S. A. Melville, P. Lichtner, H-E Wichmann, B. A. Oostra, A. C. J. W. Janssens, H. Campbell, J. F. Wilson, A. A. Hicks, P. P. Pramstaller, Z. DogasI. Rudan, M. Merrow, B. Penninx, C. P. Kyriacou, A. Metspalu, C. M. van Duijn, T. Meitinger, T. Roenneberg

Research output: Contribution to journalArticlepeer-review

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.Molecular Psychiatry advance online publication, 22 November 2011; doi:10.1038/mp.2011.142.
Original languageEnglish
Pages (from-to)122-132
Number of pages11
JournalMolecular Psychiatry
Volume18
Issue number1
Early online date22 Nov 2011
DOIs
Publication statusPublished - Jan 2013

Keywords

  • ABCC9
  • chronotype
  • Munich ChronoType Questionnaire
  • seasonality
  • sleep duration
  • SUR

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