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Nat Commun. 2018 Aug 7;9(1):3121. doi: 10.1038/s41467-018-05379-y.

Evaluation of chromatin accessibility in prefrontal cortex of individuals with schizophrenia.

Author information

1
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-17177, Stockholm, Sweden.
2
Duke Molecular Physiology Institute, Durham, NC, 27701, USA.
3
Center for Genomic and Computational Biology, Duke University, Durham, NC, 27708, USA.
4
Department of Genetics, University of North Carolina, Chapel Hill, NC, 27599-7264, USA.
5
Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
6
Research Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Roskilde, 4000, Denmark.
7
Department of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
8
Department of Genetics and Genomic Sciences and Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
9
Mental Illness Research Education and Clinical Center (MIRECC), James J. Peters VA Medical Center, Bronx, NY, 10468, USA.
10
MIRECC, JJ Peters VA Medical Center, Bronx, NY, 10468, USA.
11
Department of Psychiatry and Human Behavior, Center for Psychiatric Neuroscience, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
12
Department of Biology, Duke University, Durham, NC, 27708, USA.
13
Department of Human Genetics, University of Chicago, Chicago, IL, 60637, USA.
14
Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, 27708, USA.
15
Department of Medicine, Duke University, Durham, NC, 27708, USA.
16
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-17177, Stockholm, Sweden. pfsulliv@med.unc.edu.
17
Department of Genetics, University of North Carolina, Chapel Hill, NC, 27599-7264, USA. pfsulliv@med.unc.edu.
18
Department of Psychiatry, University of North Carolina, Chapel Hill, NC, 27599-7264, USA. pfsulliv@med.unc.edu.
19
Center for Genomic and Computational Biology, Duke University, Durham, NC, 27708, USA. greg.crawford@duke.edu.
20
Department of Pediatrics, Division of Medical Genetics, Duke University, Durham, NC, 27708, USA. greg.crawford@duke.edu.

Abstract

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.

PMID:
30087329
PMCID:
PMC6081462
DOI:
10.1038/s41467-018-05379-y
[Indexed for MEDLINE]
Free PMC Article

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