Epigenetic Pathways to Neurodevelopment Phenotypes

There is mounting evidence to support a role for developmentally regulated epigenetic variation in the molecular etiology of autism and other neuropsychiatric disorders. I will describe an analysis of dynamic DNA modifications (5mC and 5hmC) across human brain development and ageing, highlighting how the prenatal period is a time of considerable epigenomic plasticity in the brain, and the importance of neurodevelopmentally-dynamic loci in neurodevelopmental disease phenotypes. I will also describe the impact of genetic variation on gene regulation, showing how molecular quantitative trait loci (mQTLs) can be used to refine associated loci from genetic studies. Novel tools mean that it is now feasible to examine epigenetic variation across the genome in large numbers of samples, and I will give an overview of our recent epigenome-wide association studies (EWAS) of neuropsychiatric phenotypes, integrating findings with those from recent GWAS analyses. Finally, I will outline some of the issues related to epigenetic epidemiological studies of ASD and other psychiatric disorders and explore the feasibility of identifying peripheral biomarkers of phenotypes manifest in inaccessible tissues such as the brain.