LAUSR

Abstract Epigenetic processes play a key role in orchestrating transcriptional regulation during the development of the human central nervous system. We have quantified dynamic changes in DNA methylation (5mC) and DNA hydroxymethylation (5hmC) occurring during human fetal brain development, using a unique collection of human fetal brain samples spanning 23 to 184 days post-conception. We identify widespread changes in both modifications occurring during human brain development, notable sex-differences, and interactions between 5mC and 5hmC at specific sites. We also identify loci where DNA modifications in the fetal brain are associated with genetic variation, highlighting the utility of mQTLs and hmQTLs for fine-mapping GWAS loci of neurodevelopmental phenotypes. Finally, we have examined variation in both 5mC and 5hmC across multiple regions of the adult brain in neurodevelopmental phenotypes including schizophrenia and autism, identifying disease-associated DNA modifications and relating these to neurodevelopmental trajectories of gene regulation. A searchable database of our fetal brain regulatory genomic data is available as a resource to the research community at http://epigenetics.essex.ac.uk/fetalbrain2/.