A Single-Cell Atlas of DNA Methylation in Autism Spectrum Disorder Reveals Distinct Regulatory and Aging Signatures

Autism spectrum disorder (ASD) is a prevalent and heterogeneous condition that profoundly impacts health and behavior. Analysis of gene expression in the cortex broadly implicates decreased synaptic functioning in excitatory neurons and increased reactivity in glia in ASD; however, whether these phenotypes are reflected in epigenetic signatures is unknown. Here, we report on the first single-cell analysis of DNA methylation (DNAm) in ASD. We profile DNAm from over 60,000 nuclei derived from 49 donors and interpret our findings with gene expression from the same nuclei using snmCT-seq. Single-nucleus joint profiling of postmortem cortical brain samples isolated from the prefrontal cortex (PFC; Brodmann area 9, BA9) of 26 autistic male donors and 23 non-autistic male controls. 1 low RIN donor (5302) was excluded from RNA analysis. *************************************************************** Raw files for human/patient samples were not submitted to GEO due to concerns about submitting personally identifiable sequence data for open access. The raw data (controlled-access, fastq files) is going to be submitted and available through NeMO. ***************************************************************