Genome-wide methylation analysis of post-mortem cerebellum samples supports the role of peroxisomes in autism spectrum disorder. Genome-wide methylation analysis of post-mortem cerebellum samples supports the role of peroxisomes in autism spectrum disorder

We tested the hypothesis that a subset of patients with autism spectrum disorder (ASD) contains candidate genes with high DNA methylation differences (effective values) that potentially affect one of the two alleles. Genome-wide DNA methylation comparisons were made on cerebellum samples from 30 patients and 45 controls. Twelve genes with high effective values, including GSDMD, MMACHC, SLC6A5 and NKX6-2, implicated in ASD and other neuropsychiatric disorders were identified. Monoallelic promoter methylation and downregulation were observed for SERHL (serine hydrolase-like) and CAT (catalase) genes associated with peroxisome function. These data are consistent with the hypothesis implicating impaired peroxisome function/biogenesis for ASD. A similar approach holds promise for identifying rare epimutations in ASD and other complex disorders. Overall design: Genomic DNA samples isolated from 45 control and 30 autism cerebellum samples were subjected to Infinium 450 K methylation array analysis