Association of a Reproducible Epigenetic Risk Profile for Schizophrenia With Brain Methylation and Function

摘要

Key PointsQuestionCan a blood marker of epigenetic risk for schizophrenia be derived that is specific for the disease and predicts epigenetic changes in brain and disease-associated brain function? FindingsIn this case-control study, machine learning was used to identify a reproducible schizophrenia blood DNA-methylation signature that was associated with functional dorsolateral prefrontal cortex hippocampal connectivity, mapped to methylation differences found in dorsolateral prefrontal cortex hippocampal connectivity postmortem samples, and indexed biological pathways associated with synaptic function. No interactions with polygenic schizophrenia risk were found. MeaningThese findings support the presence of a systemic methylation profile in schizophrenia that is associated with established intermediate functional phenotypes as well as with epigenetic signatures in brain and should thus be useful to capture the biological effects of gene-environment interactions.