The online version of this article (doi:10.1186/s13229-017-0119-y) contains supplementary material, which is available to authorized users.
The etiology of autism, a complex, heritable, neurodevelopmental disorder, remains largely unexplained. Given the unexplained risk and recent evidence supporting a role for epigenetic mechanisms in the development of autism, we explored the role of CpG and CpH (H = A, C, or T) methylation within the autism-affected cortical brain tissue.
Reduced representation bisulfite sequencing (RRBS) was completed, and analysis was carried out in 63 post-mortem cortical brain samples (Brodmann area 19) from 29 autism-affected and 34 control individuals. Analyses to identify single sites that were differentially methylated and to identify any global methylation alterations at either CpG or CpH sites throughout the genome were carried out.
We report that while no individual site or region of methylation was significantly associated with autism after multi-test correction, methylated CpH dinucleotides were markedly enriched in autism-affected brains (~2-fold enrichment at p < 0.05 cutoff, p = 0.002).
These results further implicate epigenetic alterations in pathobiological mechanisms that underlie autism.
Additional file 1: Table S1. Functional genomic region information. TableS2. Sample information. Table S3. Differentially methylated CpG sites (p < 0.05). Table S4. Differentially methylated CpH sites (p < 0.05). Table S5. Differentially methylated CpG regions. Table S6. Differentially methylated CpH regions. (XLSX 10,803 kb)13229_2017_119_MOESM1_ESM.xlsx
Additional file 2: Figure S1. Detecting sample outliers. Figure S2. Null distributions. Figure S3. Published meQTLs help identify sample outliers. Figure S4. Cytosine summary. Figure S5. Percent methylation. Figure S6. Correlation between RRBS and 27K array data. Figure S7. Single-site differential methylation analysis. Figure S8. Methylation patterns at previously reported DMRs. Figure S9. Hypermethylation signal in CpH sites increases with methylation difference between cases and controls. Figure S10. Functional enrichment testing at histone marks from a lympoblastoid cell line (LCL). Figure S11. Power calculation curve. (PPTX 1789 kb)13229_2017_119_MOESM2_ESM.pptx
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- Exaggerated CpH methylation in the autism-affected brain
Shannon E. Ellis
Andrew B. West
Dan E. Arking
- BioMed Central