Cell-specific histone modification maps in the human frontal lobe link schizophrenia risk to the neuronal epigenome
Authors
Girdhar, KiranHoffman, Gabriel E.
Jiang, Yan
Brown, Leanne
Kundakovic, Marija
Hauberg, Mads E.
Francoeur, Nancy J.
Wang, Ying-Chih
Shah, Hardik
Kavanagh, David H.
Zharovsky, Elizabeth
Jacobov, Rivka
Wiseman, Jennifer R.
Park, Royce
Johnson, Jessica S.
Kassim, Bibi S.
Sloofman, Laura
Mattei, Eugenio
Weng, Zhiping
Sieberts, Solveig K.
Peters, Mette A.
Harris, Brent T.
Lipska, Barbara K.
Sklar, Pamela
Roussos, Panos
Akbarian, Schahram
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyProgram in Bioinformatics and Integrative Biology
Document Type
Journal ArticlePublication Date
2018-08-01Keywords
BioinformaticsComputational Biology
Genomics
Nervous System Diseases
Neuroscience and Neurobiology
Metadata
Show full item recordAbstract
Risk variants for schizophrenia affect more than 100 genomic loci, yet cell- and tissue-specific roles underlying disease liability remain poorly characterized. We have generated for two cortical areas implicated in psychosis, the dorsolateral prefrontal cortex and anterior cingulate cortex, 157 reference maps from neuronal, neuron-depleted and bulk tissue chromatin for two histone marks associated with active promoters and enhancers, H3-trimethyl-Lys4 (H3K4me3) and H3-acetyl-Lys27 (H3K27ac). Differences between neuronal and neuron-depleted chromatin states were the major axis of variation in histone modification profiles, followed by substantial variability across subjects and cortical areas. Thousands of significant histone quantitative trait loci were identified in neuronal and neuron-depleted samples. Risk variants for schizophrenia, depressive symptoms and neuroticism were significantly over-represented in neuronal H3K4me3 and H3K27ac landscapes. Our Resource, sponsored by PsychENCODE and CommonMind, highlights the critical role of cell-type-specific signatures at regulatory and disease-associated noncoding sequences in the human frontal lobe.Source
Nat Neurosci. 2018 Aug;21(8):1126-1136. doi: 10.1038/s41593-018-0187-0. Epub 2018. Jul 23. Link to article on publisher's site
DOI
10.1038/s41593-018-0187-0Permanent Link to this Item
http://hdl.handle.net/20.500.14038/25843PubMed ID
30038276Related Resources
ae974a485f413a2113503eed53cd6c53
10.1038/s41593-018-0187-0