{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T23:18:32Z","timestamp":1777418312647,"version":"3.51.4"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T00:00:00Z","timestamp":1633824000000},"content-version":"vor","delay-in-days":39,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt B"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Common genetic variation appears to largely influence risk for neuropsychiatric disorders through effects on gene regulation. It is therefore possible to shed light on the biology of these conditions by testing for enrichment of associated genetic variation within regulatory genomic regions operating in specific tissues or cell types. Here, we have used the assay for transposase\u2010accessible chromatin with high\u2010throughput sequencing (ATAC\u2010Seq) to map open chromatin (an index of active regulatory genomic regions) in bulk tissue, NeuN+ and NeuN\u2212 nuclei from the prenatal human frontal cortex, and tested enrichment of single\u2010nucleotide polymorphism (SNP) heritability for five neuropsychiatric disorders (autism spectrum disorder, attention deficit hyperactivity disorder [ADHD], bipolar disorder, major depressive disorder, and schizophrenia) within these regions. We observed significant enrichment of SNP heritability for ADHD, major depressive disorder, and schizophrenia within open chromatin regions (OCRs) mapped in bulk fetal frontal cortex, and for all five tested neuropsychiatric conditions when we restricted these sites to those overlapping histone modifications indicative of enhancers (H3K4me1) or promoters (H3K4me3) in fetal brain. SNP heritability for neuropsychiatric disorders was significantly enriched in OCRs identified in fetal frontal cortex NeuN\u2212 as well as NeuN+ nuclei overlapping fetal brain H3K4me1 or H3K4me3 sites. We additionally demonstrate the utility of our mapped OCRs for prioritizing potentially functional SNPs at genome\u2010wide significant risk loci for neuropsychiatric disorders. Our data provide evidence for an early neurodevelopmental component to a range of neuropsychiatric conditions and highlight an important role for regulatory genomic regions active within both NeuN+ and NeuN\u2212 cells of the prenatal brain.<\/jats:p>","DOI":"10.1002\/ajmg.b.32877","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T08:22:17Z","timestamp":1633940537000},"page":"376-388","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Sites of active gene regulation in the prenatal frontal cortex and their role in neuropsychiatric disorders"],"prefix":"10.1002","volume":"186","author":[{"given":"Manuela R.","family":"Kouakou","sequence":"first","affiliation":[{"name":"MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences Cardiff University  Cardiff 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J.","family":"Hill","sequence":"additional","affiliation":[{"name":"MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences Cardiff University  Cardiff UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4357-574X","authenticated-orcid":false,"given":"Nicholas J.","family":"Bray","sequence":"additional","affiliation":[{"name":"MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences Cardiff University  Cardiff 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