Interaction of circadian-regulated gene expression and DNA methylation with eleven psychiatric disorders: a Mendelian randomization study

Abstract Circadian regulation is driven by the internal circadian clock (CC), and CC-related genes have been linked to psychiatric disorders. However, a comprehensive understanding of the causal relationships between these genes and psychiatric disorders is lacking. This study used a multi-omics summary data-based Mendelian randomization (SMR) method to identify potential mechanisms connecting eleven common psychiatric disorders to CC-related genes. CC-related genes were obtained from GeneCards, and pooled GWAS data for the psychiatric disorders were collected. An integrated analysis was performed, combining GWAS data with eQTL and mQTL data from blood and brain tissues. The study identified 529 CC-related genes and found candidate causative genes for major depression, neuroticism, and schizophrenia through SMR analysis. However, no significant genetic correlations with circadian regulation were observed for other psychiatric disorders. The study hypothesized that specific DNA methylation patterns could regulate the expression of certain genes and increase the risk of major depression and schizophrenia, while decreasing the risk of neuroticism. Overall, the findings have the potential to contribute to future advancements in psychiatric disorder diagnosis.