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A KATP channel gene effect on sleep duration: from genome-wide association studies to function in Drosophila

Molecular Psychiatry volume 18, pages 122–132 (2013)Cite this article

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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.

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Acknowledgements

Our work was supported by the FP6 programme EUCLOCK (TR, KVA, MM, MT, TM, RVDMA, CPK and AM), the Dutch Science Foundation (the NWO)(MM, CvD and NA), The Hersenstichting Nederland (MM and CvD), the Rosalind Franklin Fellowships of the University of Groningen (MM), targeted Financing from the Estonian Government, the European Union through the European Regional Development Fund in the frame of Centre of Excellence in Genomics, FP7 Projects ECOGENE, and ENGAGE (AM, TE and MT-L), the Ministry of Health and Department of Educational Assistance of Italy, University and Research of the Autonomous Province of Bolzano and the South Tyrolean Sparkasse Foundation (AAH, SAM, PPP), the Geestkracht Programme of the Dutch Scientific Organization (ZON-MW) and matching funds from participating universities and mental health care organizations (BP, JvM and NV), the Genetic Association Information Network (GAIN) of the Foundation for the US National Institutes of Health (BP), the EUROSPAN through the European Commission FP6 STRP grant (HC), the Chief Scientist Office of the Scottish Government (JFW), the Royal Society (JFW), the UK Medical Research Council (CH), Republic of Croatia Ministry of Science, Education and Sports (IR), Erasmus MC, the Centre for Medical Systems Biology (CMSB1 and CMSB2), the Netherlands Genomics Initiative (NGI) (CvD and NA), the German Federal Ministry of Education and Research (BMBF) in the context of the German National Genome Research Network (NGFN-2 and NGFN-plus), the Helmholtz Center Munich - German Research Center for Environmental Health - the German Federal Ministry of Education and Research and by the State of Bavaria, the Munich Center of Health Sciences (MC Health) as part of LMUinnovativ (H-EW) and ALBAN (RA).

URLs: MACH, http://www.sph.umich.edu/csg/abecasis/MaCH; LocusZoom, http://csg.sph.umich.edu/locuszoom/; SNPs 3D, http://www.snps3d.org/; SCAN, http://www.scandb.org; METAL, http://www.sph.umich.edu/csg/abecasis/metal/index.html; PLINK, http://pngu.mgh.harvard.edu/~purcell/plink/index.shtml.

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Authors and Affiliations

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

    K V Allebrandt & T Roenneberg

  2. Department of Epidemiology and Clinical Genetics, Genetic Epidemiology unit, Erasmus MC, Rotterdam, The Netherlands

    N Amin, B A Oostra, A C J W Janssens & C M van Duijn

  3. Max-Planck-Institute of Psychiatry, Munich, Germany

    B Müller-Myhsok

  4. Estonian Genome Center and Institute of Molecular and Cell Biology of University of Tartu, Estonian Biocentre, Tartu, Estonia

    T Esko, M Teder-Laving & A Metspalu

  5. Department of Genetics, University of Leicester, Leicester, UK

    R V D M Azevedo, E W Green & C P Kyriacou

  6. Medical Research Council, Human Genetics Unit, IGMM, Edinburgh, Scotland

    C Hayward

  7. VU University Medical Center Amsterdam, Amsterdam, The Netherlands

    J van Mill, N Vogelzangs & B Penninx

  8. Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy - Affiliated Institute of the University of Lübeck, Lübeck, Germany

    S A Melville, A A Hicks & P P Pramstaller

  9. Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany

    P Lichtner & T Meitinger

  10. Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany - Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University, Munich, Germany

    H-E Wichmann

  11. Klinikum Großhadern, Munich, Germany

    H-E Wichmann

  12. Centre for Population Health Sciences, University of Edinburgh, Edinburgh, Scotland

    H Campbell, J F Wilson & I Rudan

  13. Croatian Centre for Global Health, University of Split Medical School, Split, Croatia

    Z Dogas & I Rudan

  14. Department of Molecular Chronobiology, University of Groningen, Groningen, The Netherlands

    M Merrow

  15. Centre of Medical Systems Biology, Netherlands Genomics Initiative (NGI), The Netherlands

    C M van Duijn

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  1. K V Allebrandt
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  2. N Amin
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Correspondence to T Roenneberg.

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Allebrandt, K., Amin, N., Müller-Myhsok, B. et al. A KATP channel gene effect on sleep duration: from genome-wide association studies to function in Drosophila. Mol Psychiatry 18, 122–132 (2013). https://doi.org/10.1038/mp.2011.142

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