Identifying pathways modulating sleep duration: from genomics to transcriptomics

• Published in: Scientific reports 2017-07, Vol.7 (1), p.4555-11, Article 4555
• Main Authors: Allebrandt, Karla V., Teder-Laving, Maris, Cusumano, Paola, Frishman, Goar, Levandovski, Rosa, Ruepp, Andreas, Hidalgo, Maria P. L., Costa, Rodolfo, Metspalu, Andres, Roenneberg, Till, De Pittà, Cristiano
• Format: Article
• Language: English
• Subjects: 38/39; 38/43; 38/61; 38/89; 45/22; 631/114/2401; 631/208/1515; 631/208/199; 64/24; 692/699/2743/2037; Animals; Circadian rhythms; Computational Biology; Drosophila - physiology; Epidermal growth factor receptors; ErbB protein; ErbB Receptors - metabolism; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Gene Regulatory Networks; Genes; Genome-Wide Association Study; Genomics; Gluconeogenesis; Humanities and Social Sciences; Humans; Insulin; Insulin secretion; Ion channels; Lipogenesis; Meta-Analysis as Topic; multidisciplinary; Phenotype; Polymorphism, Single Nucleotide; Science; Science (multidisciplinary); Secretion; Signal Transduction; Sleep; Sleep - physiology; Transcriptome; Tyrosine
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-04027-7

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; d Sur ). 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.