There is growing evidence that the majority of common variants associated with complex traits act through effects on gene regulation10,11. Our data add to a growing literature showing that DNA methylation is genetically influenced27, with mQTLs representing a potential mechanism linking genetic variation to complex phenotypes4,9,36,37. We find a significant enrichment of schizophrenia-associated GWAS variants in fetal brain mQTLs, indicating that common genetic variants conferring risk for schizophrenia are associated with altered DNA methylation in fetal human brain. The hypothesis that schizophrenia has an early neurodevelopmental component is supported by several lines of epidemiological and neuropathological evidence13,14. However, direct molecular evidence of schizophrenia risk factors operating in the fetal brain is scarce38,39. We have recently found that genomic loci that are differentially methylated between schizophrenia patients and unaffected controls in the adult brain are enriched at those undergoing dynamic changes in DNA methylation during human fetal brain development6,40. In the present study, we find that genetic variants exhibiting genome-wide significant association with schizophrenia12 show a four-fold enrichment amongst fetal brain mQTLs, directly implicating altered gene regulation during fetal brain development in the etiology of the disorder.
