LAUSR

Background Neuropsychiatric conditions such as schizophrenia and autism are complex disorders with a neurodevelopmental origin. Most common risk loci for these disorders are located in non-coding regions of the genome and are likely to index functional variants that alter gene regulation rather than protein structure. Identifying regulatory genomic regions active in the developing human brain will therefore be important for elucidating genetic mechanisms underpinning these conditions. Methods We sought to identify sites of open chromatin, indicative of active regulatory regions, in frontal lobe from two samples from the 2nd trimester of gestation using the Assay for Transposase-Accessible Chromatin with high throughput sequencing (ATAC-seq). Nuclei from frozen brain tissue were isolated by ultracentrifugation, followed by FACS to separate NeuN+ and Ki67+ cells. ATAC-seq libraries were sequenced on a HiSeq. 4000 and data analyzed following the ENCODE pipeline. Results We have identified regulatory genomic regions that are active in the prenatal human brain. We will test for enrichment of polygenic signal for psychiatric disorders such as schizophrenia within these regions. Discussion These data advance our understanding of gene regulation within cells from the developing human brain. Identifying risk variants for psychiatric disorders within regulatory regions active in the human fetal brain will help elucidate neurodevelopmental risk mechanisms for these conditions.