A Systems Approach Identifies Networks and Genes Linking Sleep and Stress: Implications for Neuropsychiatric Disorders

Peng Jiang, Joseph R. Scarpa, Karrie Fitzpatrick, Bojan Losic, Vance D. Gao, Ke Hao, Keith C. Summa, He S. Yang, Bin Zhang, Ravi Allada, Martha H. Vitaterna, Fred W. Turek*, Andrew Kasarskis

*Corresponding author for this work

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Sleep dysfunction and stress susceptibility are comorbid complex traits that often precede and predispose patients to a variety of neuropsychiatric diseases. Here, we demonstrate multilevel organizations of genetic landscape, candidate genes, and molecular networks associated with 328 stress and sleep traits in a chronically stressed population of 338 (C57BL/6J × A/J) F2 mice. We constructed striatal gene co-expression networks, revealing functionally and cell-type-specific gene co-regulations important for stress and sleep. Using a composite ranking system, we identified network modules most relevant for 15 independent phenotypic categories, highlighting a mitochondria/synaptic module that links sleep and stress. The key network regulators of this module are overrepresented with genes implicated in neuropsychiatric diseases. Our work suggests that the interplay among sleep, stress, and neuropathology emerges from genetic influences on gene expression and their collective organization through complex molecular networks, providing a framework for interrogating the mechanisms underlying sleep, stress susceptibility, and related neuropsychiatric disorders.

Original languageEnglish (US)
Pages (from-to)835-848
Number of pages14
JournalCell reports
Volume11
Issue number5
DOIs
StatePublished - 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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