Cell type-specific epigenetic links to schizophrenia risk in the brain.

Brain / cytology Case-Control Studies DNA Methylation Epigenesis, Genetic Humans Schizophrenia / genetics
Brain cell type DNA methylation Epigenetics Neurogenomics Neuron Oligodendrocyte Schizophrenia Transcriptome

Journal

Genome biology
ISSN: 1474-760X
Titre abrégé: Genome Biol
Pays: England
ID NLM: 100960660

Informations de publication

Date de publication:
09 07 2019
Historique:
received: 10 06 2019
accepted: 25 06 2019
entrez: 11 7 2019
pubmed: 11 7 2019
medline: 7 8 2019
Statut: epublish

Résumé

The importance of cell type-specific epigenetic variation of non-coding regions in neuropsychiatric disorders is increasingly appreciated, yet data from disease brains are conspicuously lacking. We generate cell type-specific whole-genome methylomes (N = 95) and transcriptomes (N = 89) from neurons and oligodendrocytes obtained from brain tissue of patients with schizophrenia and matched controls. The methylomes of the two cell types are highly distinct, with the majority of differential DNA methylation occurring in non-coding regions. DNA methylation differences between cases and controls are subtle compared to cell type differences, yet robust against permuted data and validated in targeted deep-sequencing analyses. Differential DNA methylation between control and schizophrenia tends to occur in cell type differentially methylated sites, highlighting the significance of cell type-specific epigenetic dysregulation in a complex neuropsychiatric disorder. Our results provide novel and comprehensive methylome and transcriptome data from distinct cell populations within patient-derived brain tissues. This data clearly demonstrate that cell type epigenetic-differentiated sites are preferentially targeted by disease-associated epigenetic dysregulation. We further show reduced cell type epigenetic distinction in schizophrenia.

Sections du résumé

BACKGROUND
The importance of cell type-specific epigenetic variation of non-coding regions in neuropsychiatric disorders is increasingly appreciated, yet data from disease brains are conspicuously lacking. We generate cell type-specific whole-genome methylomes (N = 95) and transcriptomes (N = 89) from neurons and oligodendrocytes obtained from brain tissue of patients with schizophrenia and matched controls.
RESULTS
The methylomes of the two cell types are highly distinct, with the majority of differential DNA methylation occurring in non-coding regions. DNA methylation differences between cases and controls are subtle compared to cell type differences, yet robust against permuted data and validated in targeted deep-sequencing analyses. Differential DNA methylation between control and schizophrenia tends to occur in cell type differentially methylated sites, highlighting the significance of cell type-specific epigenetic dysregulation in a complex neuropsychiatric disorder.
CONCLUSIONS
Our results provide novel and comprehensive methylome and transcriptome data from distinct cell populations within patient-derived brain tissues. This data clearly demonstrate that cell type epigenetic-differentiated sites are preferentially targeted by disease-associated epigenetic dysregulation. We further show reduced cell type epigenetic distinction in schizophrenia.

Identifiants

DOI: 10.1186/s13059-019-1747-7 PMID: 31288836 PMC: PMC6617737
pubmed: 31288836
doi: 10.1186/s13059-019-1747-7
pii: 10.1186/s13059-019-1747-7
pmc: PMC6617737
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Pagination

135

Subventions

Organisme : NIH HHS
ID : P51 OD011132
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH103517
Pays : United States
Organisme : NINDS NIH HHS
ID : R24 NS092988
Pays : United States

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Auteurs

Isabel Mendizabal (I)

School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, 30332, USA.

Stefano Berto (S)

Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX, 75390, USA.

Noriyoshi Usui (N)

Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
Center for Medical Research and Education, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.

Kazuya Toriumi (K)

Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
Schizophrenia Research Project, Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, 156-8506, Japan.

Paramita Chatterjee (P)

School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, 30332, USA.

Connor Douglas (C)

Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX, 75390, USA.

Iksoo Huh (I)

School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
College of Nursing, The Research Institute of Nursing Science, Seoul National University, Seoul, 03080, South Korea.

Hyeonsoo Jeong (H)

School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, 30332, USA.

Thomas Layman (T)

School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, 30332, USA.

Carol A Tamminga (CA)

Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX, 75390, USA.

Todd M Preuss (TM)

Division of Neuropharmacology and Neurologic Diseases, Department of Pathology, Yerkes National Primate Research Center, Emory University School of Medicine, Emory University, Atlanta, GA, 30329, USA.

Genevieve Konopka (G)

Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX, 75390, USA. Genevieve.Konopka@utsouthwestern.edu.

Soojin V Yi (SV)

School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, 30332, USA. soojinyi@gatech.edu.

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Classifications MeSH

questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Cell type-specific epigenetic links to...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études cas-témoins › Cell type-specific epigenetic links to...
questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › Cell type-specific epigenetic links to...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Cell type-specific epigenetic links to...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Cell type-specific epigenetic links to...
questionsmedicales.fr › Troubles mentaux › Schizophrénie et troubles avec traits psychotiques › Schizophrénie › Cell type-specific epigenetic links to...