Fig. 1.

Hemispheric asymmetry in DNA methylation in cortical neurons of the human brain. a Manhattan plot showing DNA methylation differences between neurons of the left and right hemisphere of the prefrontal cortex of control individuals, after adjusting for age, sex, postmortem interval, and neuronal subtype proportion. DNA methylation was mapped at enhancers and promoters of neurons from the control prefrontal cortex (n = 25 left hemispheres, 23 right). −log10(p) refers to the significance of differentially methylated cytosines, with the sign corresponding to the hemisphere side exhibiting higher DNA methylation levels. Threshold for genome-wide significance (red line) is q < 0.05, as determined by robust linear regression with contrasts. b Bar plot showing the distribution of differentially methylated cytosines (DMC) across hemispheres. The number of significant cytosine sites that show greater DNA methylation levels in the left or right hemisphere is shown. The p value represents the enrichment of cytosines with increased DNA methylation in the left hemisphere, by Fisher’s exact test. CpG and CpH site contribution to differential methylation in each hemisphere is shown. c Genomic location of DNA methylation changes involved in hemispheric asymmetry in human cortical neurons. The location of CpG (left panel) and CpH (right panel) sites with increased DNA methylation in the left or right hemisphere is shown. Inset is a close-up of the transcription start site region. d CpG and CpH involvement in inter-hemispheric DNA methylation differences. The percent number of significantly altered CpG or CpH sites differing between hemispheres (relative to background) is shown. The enrichment of cytosine context involved in hemispheric asymmetry was determined by hypergeometric test. e Top biological processes and disease pathways of genes affected by hemispheric asymmetry in DNA methylation. Pathway analysis was done by MetaCore. Threshold for significance (red dashed line) is q < 0.05