Identifying pathways modulating sleep duration: from genomics to transcriptomics

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 signall...

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Autores principales: Karla V. Allebrandt, Maris Teder-Laving, Paola Cusumano, Goar Frishman, Rosa Levandovski, Andreas Ruepp, Maria P. L. Hidalgo, Rodolfo Costa, Andres Metspalu, Till Roenneberg, Cristiano De Pittà
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/63089e19cbdc46febc44f47d63b77f62
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spelling oai:doaj.org-article:63089e19cbdc46febc44f47d63b77f622021-12-02T15:05:19ZIdentifying pathways modulating sleep duration: from genomics to transcriptomics10.1038/s41598-017-04027-72045-2322https://doaj.org/article/63089e19cbdc46febc44f47d63b77f622017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04027-7https://doaj.org/toc/2045-2322Abstract 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.Karla V. AllebrandtMaris Teder-LavingPaola CusumanoGoar FrishmanRosa LevandovskiAndreas RueppMaria P. L. HidalgoRodolfo CostaAndres MetspaluTill RoennebergCristiano De PittàNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Karla V. Allebrandt
Maris Teder-Laving
Paola Cusumano
Goar Frishman
Rosa Levandovski
Andreas Ruepp
Maria P. L. Hidalgo
Rodolfo Costa
Andres Metspalu
Till Roenneberg
Cristiano De Pittà
Identifying pathways modulating sleep duration: from genomics to transcriptomics
description 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.
format article
author Karla V. Allebrandt
Maris Teder-Laving
Paola Cusumano
Goar Frishman
Rosa Levandovski
Andreas Ruepp
Maria P. L. Hidalgo
Rodolfo Costa
Andres Metspalu
Till Roenneberg
Cristiano De Pittà
author_facet Karla V. Allebrandt
Maris Teder-Laving
Paola Cusumano
Goar Frishman
Rosa Levandovski
Andreas Ruepp
Maria P. L. Hidalgo
Rodolfo Costa
Andres Metspalu
Till Roenneberg
Cristiano De Pittà
author_sort Karla V. Allebrandt
title Identifying pathways modulating sleep duration: from genomics to transcriptomics
title_short Identifying pathways modulating sleep duration: from genomics to transcriptomics
title_full Identifying pathways modulating sleep duration: from genomics to transcriptomics
title_fullStr Identifying pathways modulating sleep duration: from genomics to transcriptomics
title_full_unstemmed Identifying pathways modulating sleep duration: from genomics to transcriptomics
title_sort identifying pathways modulating sleep duration: from genomics to transcriptomics
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/63089e19cbdc46febc44f47d63b77f62
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