DNA methylation (DNAm) signal from the planum temporale of superior temporal gyrus (STG) of forty-four subjects with schizophrenia (SZ) and forty-four non-psychiatric control (NPC) subjects was measured on the Illumina MethylationEPIC BeadChip Infinium (EPIC) array. Averaged, normalized beta-values at each site were correlated with dendritic spine density (DSD) previously measured per subject to identify site-specific DNAm-DSD correlations that met methylome-wide significance, or a suggestive-level of significance. We tested the hypothesis that DNAm correlates with DSD in human STG at several sites across the methylome and that this relationship is disrupted in SZ. DSD measures were available for 40 of the subjects with SZ and 40 of the NPC subjects. We found DNAm to correlate with DSD at more sites than expected by chance in NPC, but not SZ, subjects. In addition, we show that the slopes of the linear DNAm-DSD correlations differed between SZ and NPC subjects at more sites than expected by chance. Together, these data suggest that alterations in the intercation between DNAm and neurobiology in SZ may be a mechanism for SZ-related DSD reductions.
Overall design
A total of 96 genomic DNA samples taken from postmortem STG of subjects with SZ (N=44, with 4 subjects replicated) and NPC subjects (N=44, with 4 subjects replicated) were bisulfite converted and hybridized to the probes on the EPIC array. SZ: Schizophrenia NPC: Non-psychiatric control STG: Superior temporal gyrus (of human brain)