TY - JOUR T1 - Cell-type specific open chromatin profiling in human postmortem brain infers functional roles for non-coding schizophrenia loci JF - bioRxiv DO - 10.1101/062513 SP - 062513 AU - John F. Fullard AU - Claudia Giambartolomei AU - Mads E. Hauberg AU - Ke Xu AU - Christopher Bare AU - Joel T. Dudley AU - Manuel Mattheisen AU - Joseph K. Pickrell AU - Vahram Haroutunian AU - Panos Roussos Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/07/07/062513.abstract N2 - To better understand the role of cis regulatory elements in neuropsychiatric disorders we applied ATAC-seq to neuronal and non-neuronal nuclei isolated from frozen postmortem human brain. Most of the identified open chromatin regions (OCRs) are differentially accessible between neurons and non-neurons, and show enrichment with known cell type markers, promoters and enhancers. Relative to those of non-neurons, neuronal OCRs are more evolutionarily conserved and are enriched in distal regulatory elements. Our data reveals sex differences in chromatin accessibility and identifies novel OCRs that escape X chromosome inactivation, with implications for intellectual disability. Transcription factor footprinting analysis identifies differences in the regulome between neuronal and non-neuronal cells and ascribes putative functional roles to 16 non-coding schizophrenia risk variants. These results represent the first analysis of cell-type-specific OCRs and TF binding sites in postmortem human brain and further our understanding of the regulome and the impact of neuropsychiatric disease-associated genetic risk variants. ER -