A systems approach identifies networks and genes linking sleep and stress: implications for neuropsychiatric disorders.

TitleA systems approach identifies networks and genes linking sleep and stress: implications for neuropsychiatric disorders.
Publication TypeJournal Article
Year of Publication2015
AuthorsJiang P, Scarpa JR, Fitzpatrick K, Losic B, Gao VD, Hao K, Summa KC, Yang HS, Zhang B, Allada R, Vitaterna MH, Turek FW, Kasarskis A
JournalCell Rep
Volume11
Issue5
Pagination835-48
Date Published2015 May 05
ISSN2211-1247
KeywordsAnimals, Bayes Theorem, Gene Regulatory Networks, Mental Disorders, Mice, Inbred C57BL, Microfilament Proteins, Phenotype, Quantitative Trait Loci, Sleep, Stress, Psychological, Transcriptome
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.

DOI10.1016/j.celrep.2015.04.003
Alternate JournalCell Rep
PubMed ID25921536
PubMed Central IDPMC4797932
Grant ListF30 MH106293 / MH / NIMH NIH HHS / United States
T32 HL007909 / HL / NHLBI NIH HHS / United States
F30MH106293 / MH / NIMH NIH HHS / United States
Related Faculty: 
He Sarina Yang, M.D., Ph.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700