Evaluation of chromatin accessibility in prefrontal cortex of individuals with schizophrenia

Schizophrenia genome-wide association studies have identified >150 regions of the genome associated with disease risk, yet there is little evidence that coding mutations contribute to this disorder. To explore the mechanism of non-coding regulatory elements in schizophrenia, we performed ATAC-seq...

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Bibliographic Details
Published in:Nature communications Vol. 9; no. 1; pp. 3121 - 15
Main Authors: Bryois, Julien, Garrett, Melanie E., Song, Lingyun, Safi, Alexias, Giusti-Rodriguez, Paola, Johnson, Graham D., Shieh, Annie W., Buil, Alfonso, Fullard, John F., Roussos, Panos, Sklar, Pamela, Akbarian, Schahram, Haroutunian, Vahram, Stockmeier, Craig A., Wray, Gregory A., White, Kevin P., Liu, Chunyu, Reddy, Timothy E., Ashley-Koch, Allison, Sullivan, Patrick F., Crawford, Gregory E.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 07.08.2018
Nature Publishing Group
Nature Portfolio
Subjects:
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38
45
631/337/100/102
631/378/1689/1799
Accessibility
Age
Aged
Aged, 80 and over
Brain
Brain - physiopathology
Chromatin
Chromatin - chemistry
Conserved sequence
Female
Gene Expression Profiling
Gene mapping
Genome-wide association studies
Genome-Wide Association Study
Genomes
Health risks
Heritability
High-Throughput Nucleotide Sequencing
Humanities and Social Sciences
Humans
Male
Mental disorders
Middle Aged
multidisciplinary
Mutation
Non-coding RNA
Polymorphism, Single Nucleotide
Prefrontal cortex
Prefrontal Cortex - metabolism
Quantitative Trait Loci
Regulatory sequences
Risk
Schizophrenia
Schizophrenia - genetics
Schizophrenia - metabolism
Science
Science (multidisciplinary)
Sequence Analysis, DNA
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary:Schizophrenia genome-wide association studies have identified >150 regions of the genome associated with disease risk, yet there is little evidence that coding mutations contribute to this disorder. To explore the mechanism of non-coding regulatory elements in schizophrenia, we performed ATAC-seq on adult prefrontal cortex brain samples from 135 individuals with schizophrenia and 137 controls, and identified 118,152 ATAC-seq peaks. These accessible chromatin regions in the brain are highly enriched for schizophrenia SNP heritability. Accessible chromatin regions that overlap evolutionarily conserved regions exhibit an even higher heritability enrichment, indicating that sequence conservation can further refine functional risk variants. We identify few differences in chromatin accessibility between cases and controls, in contrast to thousands of age-related differential accessible chromatin regions. Altogether, we characterize chromatin accessibility in the human prefrontal cortex, the effect of schizophrenia and age on chromatin accessibility, and provide evidence that our dataset will allow for fine mapping of risk variants. Chromatin accessibility may be altered in disease states. Here the authors carry out ATAC-seq on a large number of samples of dorsolateral prefrontal cortex from individuals with schizophrenia, and healthy controls.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-018-05379-y