We next tested for significant enrichment between the CpGs that display epigenetic differences associated with the prenatal-postnatal transition and genomic loci associated with schizophrenia risk in the latest Psychiatric Genomics Consortium (PGC) genome-wide association study (GWAS)25. Of the 456,513 probes on the Illumina 450k used in differential methylation analysis, 5,476 were within the 108 genome-wide significant risk loci (specifically, the linkage disequilibrium, LD, blocks defined by the loci). These particular CpGs were more likely to be differentially methylated across the fetal-postnatal transition (2,903/5,476, 53.0%, in the loci compared to 228,512/451,037, 50.7% outside; OR=1.10, χ2 p-value=5.75×10−4, Supplementary Table 7). This association was driven by a majority subset of 3,607 CpGs in the PGC regions that were relatively more highly methylated in fetal compared to post-natal life (1,848/3,607; 51.2%, versus 126,674/272,242; 46.5%, OR = 1.21, p-value=2.03×10−8) – the subset of CpGs more highly methylated in postnatal life were not relatively enriched in the SZ GWAS loci (OR=0.98, p=0.67).
