CONVERGENT METHYLOMIC SIGNATURES BETWEEN AUTISM ASSOCIATED WITH DUPLICATIONS OF CHROMOSOME 15Q AND IDIOPATHIC AUTISM

Background Autism Spectrum Disorder (ASD) includes a spectrum of genetically and clinically complex neurodevelopmental disorders. Findings from recent discordant monozygotic twins and post-mortem brain studies suggest that altered epigenetic processes, including DNA methylation and histone acetylation, are involved in the etiology of ASD. This study presents, to our knowledge, the largest post-mortem genome-wide DNA methylation analyses of autism patients, including idiopathic ASD and chromosome 15q11.2-13.1 duplication syndrome (dup15q) carriers, and matched controls. Methods We performed methylomic profiling in human post-mortem brain tissues using samples from three brain regions (dorsolateral prefrontal cortex, primary auditory cortex and cerebellum) of idiopathic autism cases, dup15q cariers and matched controls using the Illumina Infinium HumanMethylation450 array. Following stringent quality control and data pre-processing ASD-associated differential methylation analyses were performed at both probe-wise and region-wise levels. Results Our analyses revealed ASD-associated dysregulation of DNA methylation at multiple loci, with a large number of cross-cortex significant differentially methylated probes. In addition, although the differential methylation observed in dup15q samples were much more pronounced than those from iASD samples, we observed a convergent of methylomic signatures between autism associated with duplications of chromosome 15q and idiopathic autism. Discussion This epigenome-wide study of autism using post-mortem tissues represents the most comprehensive study to date. Findings from this study further support a role of altered epigenetics signatures in ASD and provide novel insight that idiopathic ASD and a genetically defined form of ASD (i.e. dup15q) carry similar underlying epigenetics changes.