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Sci Rep. 2017 Jul 4;7(1):4555. doi: 10.1038/s41598-017-04027-7.

Identifying pathways modulating sleep duration: from genomics to transcriptomics.

Author information

1
Institute of Medical Psychology, Ludwig-Maximilians-University, Munich, Germany. karlaviviani.allebrandt@gmail.com.
2
Estonian Genome Center and Institute of Molecular and Cell Biology of University of Tartu, Estonian Biocentre, Tartu, Estonia.
3
Department of Biology, University of Padova, Padova, Italy.
4
Institute for Bioinformatics and Systems Biology (IBIS); Helmholtz Center Munich, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
5
Departamento de Psiquiatria e Medicina Legal, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
6
Institute of Medical Psychology, Ludwig-Maximilians-University, Munich, Germany.

Abstract

Recognizing that insights into the modulation of sleep duration can emerge by exploring the functional relationships among genes, we used this strategy to explore the genome-wide association results for this trait. We detected two major signalling pathways (ion channels and the ERBB signalling family of tyrosine kinases) that could be replicated across independent GWA studies meta-analyses. To investigate the significance of these pathways for sleep modulation, we performed transcriptome analyses of short sleeping flies' heads (knockdown for the ABCC9 gene homolog; dSur). We found significant alterations in gene-expression in the short sleeping knockdowns versus controls flies, which correspond to pathways associated with sleep duration in our human studies. Most notably, the expression of Rho and EGFR (members of the ERBB signalling pathway) genes was down- and up-regulated, respectively, consistently with the established role of these genes for sleep consolidation in Drosophila. Using a disease multifactorial interaction network, we showed that many of the genes of the pathways indicated to be relevant for sleep duration had functional evidence of their involvement with sleep regulation, circadian rhythms, insulin secretion, gluconeogenesis and lipogenesis.

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