Evaluation of chromatin accessibility in prefrontal cortex of individuals with schizophrenia

Julien Bryois, Melanie E. Garrett, Lingyun Song, Alexias Safi, Paola Giusti-Rodriguez, Graham D. Johnson, Annie W. Shieh, Alfonso Buil, John F. Fullard, Panos Roussos, Pamela Sklar, Schahram Akbarian, Vahram Haroutunian, Craig A. Stockmeier, Gregory A. Wray, Kevin P. White, Chunyu Liu, Timothy E. Reddy, Allison Ashley-Koch, Patrick F. Sullivan () and Gregory E. Crawford ()
Additional contact information
Julien Bryois: Karolinska Institutet
Melanie E. Garrett: Duke Molecular Physiology Institute
Lingyun Song: Duke University
Alexias Safi: Duke University
Paola Giusti-Rodriguez: University of North Carolina
Graham D. Johnson: Duke University
Annie W. Shieh: SUNY Upstate Medical University
Alfonso Buil: Mental Health Center Sct. Hans
John F. Fullard: Icahn School of Medicine at Mount Sinai
Panos Roussos: Icahn School of Medicine at Mount Sinai
Pamela Sklar: Icahn School of Medicine at Mount Sinai
Schahram Akbarian: Icahn School of Medicine at Mount Sinai
Vahram Haroutunian: Icahn School of Medicine at Mount Sinai
Craig A. Stockmeier: University of Mississippi Medical Center
Gregory A. Wray: Duke University
Kevin P. White: University of Chicago
Chunyu Liu: SUNY Upstate Medical University
Timothy E. Reddy: Duke University
Allison Ashley-Koch: Duke Molecular Physiology Institute
Patrick F. Sullivan: Karolinska Institutet
Gregory E. Crawford: Duke University

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-05379-y

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