Title | A systems approach identifies networks and genes linking sleep and stress: implications for neuropsychiatric disorders. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Jiang 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 |
Journal | Cell Rep |
Volume | 11 |
Issue | 5 |
Pagination | 835-48 |
Date Published | 2015 May 05 |
ISSN | 2211-1247 |
Keywords | Animals, 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. |
DOI | 10.1016/j.celrep.2015.04.003 |
Alternate Journal | Cell Rep |
PubMed ID | 25921536 |
PubMed Central ID | PMC4797932 |
Grant List | F30 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.