Conversely, homogenate brain tissue appears to represent a powerful tool for better understanding how genotypes identified in large population-based GWAS may manifest risk for neurodevelopmental and other brain disorders. Indeed, many meQTLs identified in the DLPFC during adult life appear consistent in fetal life – and reach genome-wide significance in larger fetal samples29 - despite very different cellular compositions, suggesting that many of these variations serve conserved regulatory roles in multiple cell types. Furthermore, DNAm levels may be a more proximal read out of genetic variation than gene expression levels42 – here we identified that 62/104 (59.6%) genome-wide significant genetic loci for schizophrenia risk associated with local DNAm levels, compared to a report suggesting that only 18/108 (16.7%) GWAS-positive loci are eQTLs across the human brain (see Supplementary Table 4, Worksheet 2 in Schizophrenia Working Group of the Psychiatric Genomics25).
