We lastly performed a differential methylation analysis for schizophrenia diagnosis at the single CpG level by comparing 191 adult patients with schizophrenia to the 240 (of 335) non-psychiatric controls all with ages greater than 16 (Supplementary Table 1). The schizophrenia patients had relatively typical age of onset (mean = 22.5 years, SD = 7.0 years) and the majority were on anti-psychotic medications at the time of death (64.0%), assessed via chart review and/or toxicology on brain tissue (see Methods). There were similar proportions of race, sex, and causes of death (other than suicide) in the control and schizophrenia group but the patients were more likely to be older and smoke, have a lower tissue pH and longer postmortem interval (PMI). We further note these patients had a relatively young average age at death compared to other post-mortem samples32, potentially reducing the cumulative impact of chronicity, smoking and antipsychotics on DNAm levels. In these adult samples, we did not identify significant differences in composition of any estimated cell types between cases and controls (Supplementary Figure 9A), though cellular composition explained a large component of variability in the data (Supplementary Figure 9B).
