A recent paper identified 4 significant CpGs differentially methylated in a smaller sample of brains of schizophrenia patients (N=20) and controls (N=23) across a discovery and replication cohort36 but we found only one of these CpGs that was directionally consistent and marginally significant in our much larger dataset (near GSDMD (cg26173173) at p=0.02). We failed to replicate the other three CpGs - cg24803255 and cg08171022 were also higher and lower in cases compared to controls, respectively, but neither were significant (p=0.32 and p=0.97, respectively), and cg00903099 was marginally significant (p=0.02) but higher in cases compared to controls in our data rather than the reported hypomethylation. Conversely, only one of our CpGs was marginally significant (at p < 0.05) and directionally consistent in both their discovery and replication datasets when treating each separately, potentially highlighting uncertainties in case control analyses of DNAm, including heterogeneity in the clinical disorder, differing epiphenomena related to diagnosis and illness state, and differences in the ascertained tissue for postmortem human brain studies.
