TY - JOUR
T1 - A Systems Approach Identifies Networks and Genes Linking Sleep and Stress
T2 - Implications for Neuropsychiatric Disorders
AU - Jiang, Peng
AU - Scarpa, Joseph R.
AU - Fitzpatrick, Karrie
AU - Losic, Bojan
AU - Gao, Vance D.
AU - Hao, Ke
AU - Summa, Keith C.
AU - Yang, He S.
AU - Zhang, Bin
AU - Allada, Ravi
AU - Vitaterna, Martha H.
AU - Turek, Fred W.
AU - Kasarskis, Andrew
N1 - Funding Information:
This work is supported by the Defense Advanced Research Projects Agency, The U.S. Army Research Laboratory, and the U.S. Army Research Office under government contract/grant numbers W911NF101006. The views, opinions, and/or findings contained in this work are those of the authors and should not be interpreted as representing the official views or policies, either expressed or implied, of the Defense Advanced Research Projects Agency or the Department of Defense. J.R.S. is also supported by the National Institute of Mental Health of the NIH under Award Number F30MH106293. The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The authors also thank Dr. Tingting Liu and Christopher J. Olker for their assistance in data and tissue collection and Julia King for her contribution to the illustrations.
Publisher Copyright:
© 2015 The Authors.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84933677987&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2015.04.003
DO - 10.1016/j.celrep.2015.04.003
M3 - Article
C2 - 25921536
AN - SCOPUS:84933677987
SN - 2211-1247
VL - 11
SP - 835
EP - 848
JO - Cell Reports
JF - Cell Reports
IS - 5
ER -