Dataset Information

Identification of causal genes, networks, and transcriptional regulators of REM sleep and wake.

ABSTRACT:

Study objective

Sleep-wake traits are well-known to be under substantial genetic control, but the specific genes and gene networks underlying primary sleep-wake traits have largely eluded identification using conventional approaches, especially in mammals. Thus, the aim of this study was to use systems genetics and statistical approaches to uncover the genetic networks underlying 2 primary sleep traits in the mouse: 24-h duration of REM sleep and wake.

Design

Genome-wide RNA expression data from 3 tissues (anterior cortex, hypothalamus, thalamus/midbrain) were used in conjunction with high-density genotyping to identify candidate causal genes and networks mediating the effects of 2 QTL regulating the 24-h duration of REM sleep and one regulating the 24-h duration of wake.

Setting

Basic sleep research laboratory.

Patients or participants

Male [C57BL/6J × (BALB/cByJ × C57BL/6J*) F1] N(2) mice (n = 283).

Interventions

None.

Measurements and results

The genetic variation of a mouse N2 mapping cross was leveraged against sleep-state phenotypic variation as well as quantitative gene expression measurement in key brain regions using integrative genomics approaches to uncover multiple causal sleep-state regulatory genes, including several surprising novel candidates, which interact as components of networks that modulate REM sleep and wake. In particular, it was discovered that a core network module, consisting of 20 genes, involved in the regulation of REM sleep duration is conserved across the cortex, hypothalamus, and thalamus. A novel application of a formal causal inference test was also used to identify those genes directly regulating sleep via control of expression.

Conclusion

Systems genetics approaches reveal novel candidate genes, complex networks and specific transcriptional regulators of REM sleep and wake duration in mammals.

SUBMITTER: Millstein J

PROVIDER: S-EPMC3198032 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Publications

Identification of causal genes, networks, and transcriptional regulators of REM sleep and wake.

Millstein Joshua J Winrow Christopher J CJ Kasarskis Andrew A Owens Joseph R JR Zhou Lili L Summa Keith C KC Fitzpatrick Karrie K Zhang Bin B Vitaterna Martha H MH Schadt Eric E EE Renger John J JJ Turek Fred W FW

Sleep 20111101 11

<h4>Study objective</h4>Sleep-wake traits are well-known to be under substantial genetic control, but the specific genes and gene networks underlying primary sleep-wake traits have largely eluded identification using conventional approaches, especially in mammals. Thus, the aim of this study was to use systems genetics and statistical approaches to uncover the genetic networks underlying 2 primary sleep traits in the mouse: 24-h duration of REM sleep and wake.<h4>Design</h4>Genome-wide RNA expre ...[more]

PMID: 22043117

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Project description:Study objectivesREM sleep behavior disorder (RBD) is associated with antidepressant treatment, especially in younger patients; but quantitative REM sleep without atonia (RSWA) analyses of psychiatric RBD patients remain limited. We analyzed RSWA in adults receiving antidepressants, with and without RBD.DesignWe comparatively analyzed visual, manual, and automated RSWA between RBD and control groups. RSWA metrics were compared between groups, and regression was used to explore associations with clinical variables.SettingTertiary-care sleep center.ParticipantsParticipants included traditional RBD without antidepressant treatment (n = 30, 15 Parkinson disease [PD-RBD] and 15 idiopathic); psychiatric RBD receiving antidepressants (n = 30); and adults without RBD, including antidepressant-treated psychiatric (n = 30), untreated psychiatric (n = 15), and OSA (n = 60) controls.InterventionsN/A.Measurements and resultsRSWA was highest in traditional and psychiatric RBD, intermediate in treated psychiatric controls, and lowest in untreated psychiatric and OSA controls (P < 0.01). RSWA distribution and type also differed between antidepressant-treated patients having higher values in anterior tibialis, and PD-RBD with higher submentalis and tonic RSWA. Psychiatric RBD had significantly younger age at onset than traditional RBD patients (P < 0.01).ConclusionsAntidepressant treatment was associated with elevated REM sleep without atonia (RSWA) even without REM sleep behavior disorder (RBD), suggesting that antidepressants, not depression, promote RSWA. Differences in RSWA distribution and type were also seen, with higher anterior tibialis RSWA in antidepressant-treated patients and higher tonic RSWA in Parkinson disease-RBD patients, which could aid distinction between RBD subtypes. These findings suggest that antidepressants may mediate different RSWA mechanisms or, alternatively, that RSWA type and distribution evolve during progressive neurodegeneration. Further prospective RSWA analyses are necessary to clarify the relationships between antidepressant treatment, psychiatric disease, and RBD.

Dataset Information

Identification of causal genes, networks, and transcriptional regulators of REM sleep and wake.

Study objective

Design

Setting

Patients or participants

Interventions

Measurements and results

Conclusion

Publications

Identification of causal genes, networks, and transcriptional regulators of REM sleep and wake.

Similar Datasets

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