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Homo sapiens

ABSTRACT: DNA methylation analysis of prefrontal cortex of patients with bipolar disorder by RRBS.

PROVIDER: PRJDB8773 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	DRR190841_1.fastq.gz	Fastqsanger.gz
	DRR190841_2.fastq.gz	Fastqsanger.gz
	DRR190843_1.fastq.gz	Fastqsanger.gz
	DRR190843_2.fastq.gz	Fastqsanger.gz

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Transcription profiling of human brain tissue from subjects with bipolar disorder and healthy controls

Project description:Bipolar affective disorder is a severe psychiatric disorder with a strong genetic component but unknown pathophysiology. We used microarray technology (Affymetrix HG-U133A GeneChips) to determine the expression of approximately 22 000 mRNA transcripts in post-mortem brain tissue (dorsolateral prefrontal cortex) from patients with bipolar disorder and matched healthy controls. A cohort of 70 subjects was investigated and the final analysis included 30 bipolar and 31 control subjects. Differences between disease and control groups were identified using a rigorous statistical analysis with correction for confounding variables and multiple testing.

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Project description:Background: Schizophrenia is a severe neuropsychiatric disorder that is hypothesized to result from disturbances in early brain development, and there is mounting evidence to support a role for developmentally-regulated epigenetic variation in the molecular etiology of the disorder. Here, we describe a systematic study of schizophrenia-associated methylomic variation in the adult brain and its relationship to changes in DNA methylation across human fetal brain development. Results: We profile methylomic variation in matched prefrontal cortex and cerebellum brain tissue from schizophrenia patients and controls, identifying disease-associated differential DNA methylation at multiple loci, particularly in the prefrontal cortex, and confirming these differences in an independent set of adult brain samples. Our data reveal discrete modules of co-methylated loci associated with schizophrenia that are enriched for genes involved in neurodevelopmental processes and include loci implicated by genetic studies of the disorder. Methylomic data from human fetal cortex samples, spanning 23 to 184 days post-conception, indicates that disease-associated differentially methylated positions are significantly enriched for loci at which DNA methylation is dynamically altered during human fetal brain development. Conclusions: Our data support the hypothesis that schizophrenia has an important early neurodevelopmental component, and suggest that epigenetic mechanisms may mediate these effects. 33 post-mortem brain (prefrontal cortex) samples (18 schizophrenia cases and 15 controls) were obtained from Douglas Bell-Canada Brain Bank (DBCBB), Montreal, Canada. Bisulfite converted DNA from these samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip v1.0.

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