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Brief Report: A Gene Enrichment Approach Applied to Sleep and Autism

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Abstract

Sleep disorders (SD) are common in autism spectrum disorder (ASD), yet relatively little is known about the potential genetic mechanisms involved in SD and ASD comorbidity. The current study begins to fill this gap with a gene enrichment study that (1) identifies risk genes that contribute to both SD and ASD which implicate circadian entrainment, melatonin synthesis, and several genetic syndromes. An over-representation analysis identified several enriched pathways that suggest dopamine and serotonin synapses as potential shared SD and ASD mechanisms. This overlapping gene set and the highlighted biological pathways may serve as a preliminary stepping-stone for new genetic investigations of SD and ASD comorbidity.

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References

  • Allik, H., Larsson, J.-O., & Smedje, H. (2008). Sleep patterns in school-age children with Asperger syndrome or high-functioning autism: A follow-up study. Journal of Autism and Developmental Disorders, 38(9), 1625–1633.

    Article  Google Scholar 

  • Baker, E. K., & Richdale, A. L. (2017). Examining the behavioural sleep-wake rhythm in adults with autism spectrum disorder and no comorbid intellectual disability. Journal of Autism and Developmental Disorders, 47(4), 1207–1222.

    Article  Google Scholar 

  • Cortesi, F., Giannotti, F., Ivanenko, A., & Johnson, K. (2010). Sleep in children with autistic spectrum disorder. Sleep Medicine, 11(7), 659–664.

    Article  Google Scholar 

  • Ezkurdia, I., Juan, D., Rodriguez, J. M., Frankish, A., Diekhans, M., Harrow, J., … Tress, M. L. (2014). Multiple evidence strands suggest that there may be as few as 19,000 human protein-coding genes. Human Molecular Genetics, 23(22), 5866–5878. https://doi.org/10.1093/hmg/ddu309.

    Article  PubMed  PubMed Central  Google Scholar 

  • Godbout, R., Bergeron, C., Limoges, E., Stip, E., & Mottron, L. (2000). A laboratory study of sleep in Asperger’s syndrome. NeuroReport, 11(1), 127–130.

    Article  Google Scholar 

  • Godbout, R., Bergeron, C., Stip, E., & Mottron, L. (1998). A laboratory study of sleep and dreaming in a case of Asperger’s syndrome. Dreaming, 8(2), 75–88. https://doi.org/10.1023/B:Drem.0000005898.95212.58.

    Article  Google Scholar 

  • Horder, J., Petrinovic, M. M., Mendez, M. A., Bruns, A., Takumi, T., Spooren, W., … Murphy, D. G. (2018). Glutamate and GABA in autism spectrum disorder-a translational magnetic resonance spectroscopy study in man and rodent models. Translational Psychiatry, 8(1), 106. https://doi.org/10.1038/s41398-018-0155-1.

    Article  PubMed  PubMed Central  Google Scholar 

  • Jin, L., Zuo, X. Y., Su, W. Y., Zhao, X. L., Yuan, M. Q., Han, L. Z., … Rao, S. Q. (2014). Pathway-based analysis tools for complex diseases: A review. Genomics Proteomics Bioinformatics, 12(5), 210–220. https://doi.org/10.1016/j.gpb.2014.10.002.

    Article  PubMed  PubMed Central  Google Scholar 

  • Jonsson, L., Ljunggren, E., Bremer, A., Pedersen, C., Landén, M., Thuresson, K., … Melke, J. (2010). Mutation screening of melatonin-related genes in patients with autism spectrum disorders. BMC Medical Genomics, 3(1), 10. https://doi.org/10.1186/1755-8794-3-10.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kamburov, A., Pentchev, K., Galicka, H., Wierling, C., Lehrach, H., & Herwig, R. (2011). ConsensusPathDB: Toward a more complete picture of cell biology. Nucleic Acids Research, 39, D712–D717. https://doi.org/10.1093/nar/gkq1156.

    Article  PubMed  Google Scholar 

  • Kamburov, A., Wierling, C., Lehrach, H., & Herwig, R. (2009). ConsensusPathDB—a database for integrating human functional interaction networks. Nucleic Acids Research, 37(Database issue), D623–D628. https://doi.org/10.1093/nar/gkn698.

    Article  PubMed  Google Scholar 

  • Krakowiak, P., Goodlin-Jones, B., Hertz-Picciotto, I., Croen, L. A., & Hansen, R. L. (2008). Sleep problems in children with autism spectrum disorders, developmental delays, and typical development: A population-based study. Journal of Sleep Research, 17(2), 197–206.

    Article  Google Scholar 

  • Kumar, D., Dedic, N., Flachskamm, C., Voule, S., Deussing, J. M., & Kimura, M. (2015). Cacna1c (Cav1.2) modulates electroencephalographic rhythm and rapid eye movement sleep recovery. Sleep, 38(9), 1371–1380. https://doi.org/10.5665/sleep.4972.

    Article  PubMed  PubMed Central  Google Scholar 

  • Limoges, É, Mottron, L., Bolduc, C., Berthiaume, C., & Godbout, R. (2005). Atypical sleep architecture and the autism phenotype. Brain, 128(5), 1049–1061.

    Article  Google Scholar 

  • Marceau, K., & Abel, E. A. (2018). Mechanisms of cortisol—Substance use development associations: Hypothesis generation through gene enrichment analysis. Neuroscience and Biobehavioral Reviews, 92, 128–139. https://doi.org/10.1016/j.neubiorev.2018.05.020.

    Article  PubMed  PubMed Central  Google Scholar 

  • Muller, C. L., Anacker, A. M. J., & Veenstra-VanderWeele, J. (2016). The serotonin system in autism spectrum disorder: From biomarker to animal models. Neuroscience, 321, 24–41. https://doi.org/10.1016/j.neuroscience.2015.11.010.

    Article  PubMed  Google Scholar 

  • Nicholas, B., Rudrasingham, V., Nash, S., Kirov, G., Owen, M. J., & Wimpory, D. C. (2007). Association of Per1 and Npas2 with autistic disorder: support for the clock genes/social timing hypothesis. Molelcular Psychiatry, 12(6), 581–592.

    Google Scholar 

  • Paval, D. (2017). A dopamine hypothesis of autism spectrum disorder. Developmental Neuroscience, 39(5), 355–360. https://doi.org/10.1159/000478725.

    Article  PubMed  Google Scholar 

  • Richdale, A. L., & Baglin, C. L. (2015). Self-report and caregiver-report of sleep and psychopathology in children with high-functioning autism spectrum disorder: A pilot study. Developmental Neurorehabilitation, 18(4), 272–279.

    Article  Google Scholar 

  • Richdale, A. L., & Schreck, K. A. (2009). Sleep problems in autism spectrum disorders: Prevalence, nature, & possible biopsychosocial aetiologies. Sleep Medicine Reviews, 13(6), 403–411.

    Article  Google Scholar 

  • Schmutz, I., Chavan, R., Ripperger, J. A., Maywood, E. S., Langwieser, N., Jurik, A., … Albrecht, U. (2014). A specific role for the REV-ERBalpha-controlled L-type voltage-gated calcium channel CaV1.2 in resetting the circadian clock in the late night. Journal of Biological Rhythms, 29(4), 288–298. https://doi.org/10.1177/0748730414540453.

    Article  PubMed  PubMed Central  Google Scholar 

  • Souders, M. C., Zavodny, S., Eriksen, W., Sinko, R., Connell, J., Kerns, C., … Pinto-Martin, J. (2017). Sleep in children with autism spectrum disorder. Current Psychiatry Report, 19(6), 34. https://doi.org/10.1007/s11920-017-0782-x.

    Article  Google Scholar 

  • Tani, P., Lindberg, N., Nieminen-von Wendt, T., von Wendt, L., Alanko, L., Appelberg, B., & Porkka-Heiskanen, T. (2003). Insomnia is a frequent finding in adults with Asperger syndrome. BMC Psychiatry, 3, 12. https://doi.org/10.1186/1471-244X-3-12.

    Article  PubMed  PubMed Central  Google Scholar 

  • Tani, P., Lindberg, N., Nieminen-von Wendt, T., von Wendt, L., Virkkala, J., Appelberg, B., & Porkka-Heiskanen, T. (2004). Sleep in young adults with Asperger syndrome. Neuropsychobiology, 50(2), 147–152.

    Article  Google Scholar 

  • Tordjman, S., Najjar, I., Bellissant, E., Anderson, G. M., Barburoth, M., Cohen, D., … Vernay-Leconte, J. (2013). Advances in the research of melatonin in autism spectrum disorders: Literature review and new perspectives. International Journal of Molecular Sciences, 14(10), 20508–20542. https://doi.org/10.3390/ijms141020508.

    Article  PubMed  PubMed Central  Google Scholar 

  • Veatch, O. J., Goldman, S. E., Adkins, K. W., & Malow, B. A. (2015). Melatonin in children with autism spectrum disorders: How does the evidence fit together? Journal of Nature and Science, 1(7), e125.

    PubMed  PubMed Central  Google Scholar 

  • Veatch, O. J., Pendergast, J. S., Allen, M. J., Leu, R. M., Johnson, C. H., Elsea, S. H., & Malow, B. A. (2015). Genetic variation in melatonin pathway enzymes in children with autism spectrum disorder and comorbid sleep onset delay. Journal of Autism and Developmental Disorders, 45(1), 100–110.

    Article  Google Scholar 

  • Volkow, N., Tomasi, D., Wang, G., Telang, F., Fowler, J., Logan, J., … Ferre, S. (2012). Evidence that sleep deprivation downregulates dopamine D2R in ventral striatum in the human brain. Journal of Neuroscience, 32(19), 6711–6717. https://doi.org/10.1523/JNEUROSCI.0045-12.2012.

    Article  PubMed  Google Scholar 

  • Xu, L.-M., Li, J.-R., Huang, Y., Zhao, M., Tang, X., & Wei, L. (2011). AutismKB: An evidence-based knowledgebase of autism genetics. Nucleic Acids Research, 40(D1), D1016–D1022.

    Article  Google Scholar 

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Funding

This study was funded in part by The National Institute on Drug Abuse; Grant number: K01 DA039288 (PI: Marceau).

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Authors and Affiliations

  1. Department of Human Development and Family Studies, Purdue University, 1202 West State Street, West Lafayette, IN, USA

    Emily A. Abel, A. J. Schwichtenberg, Olivia R. Mannin & Kristine Marceau

  2. Yale Child Study Center, Yale University, New Haven, CT, USA

    Emily A. Abel

Authors
  1. Emily A. Abel
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  2. A. J. Schwichtenberg
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  3. Olivia R. Mannin
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  4. Kristine Marceau
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Contributions

EAA and ORM created the sleep gene set, under the supervision of KM. EAA and KM conducted analyses. EAA and AJS drafted the initial manuscript. AJS provided content expertise in sleep and autism, while KM provided content expertise in genetics and gene enrichment methods. All authors provided critical feedback on the manuscript throughout initial drafting and revision stages.

Corresponding author

Correspondence to Emily A. Abel.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Abel, E.A., Schwichtenberg, A.J., Mannin, O.R. et al. Brief Report: A Gene Enrichment Approach Applied to Sleep and Autism. J Autism Dev Disord 50, 1834–1840 (2020). https://doi.org/10.1007/s10803-019-03921-5

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  • DOI: https://doi.org/10.1007/s10803-019-03921-5

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