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

Author:
Mendizabal, Isabel, Berto, Stefano, Usui, Noriyoshi, Toriumi, Kazuya, Chatterjee, Paramita, Douglas, Connor, Huh, Iksoo, Jeong, Hyeonsoo, Layman, Thomas, Tamminga, Carol A., Preuss, Todd M., Konopka, Genevieve, Yi, Soojin V.
Source:
Genome biology 2019 v.20 no.1 pp. 135
ISSN:
1474-760X
Subject:
DNA methylation, brain, epigenetics, high-throughput nucleotide sequencing, neurons, oligodendroglia, patients, risk, schizophrenia, tissues, transcriptome
Abstract:
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.
Agid:
6504278