Functional analysis of evolutionary human methylated regions in schizophrenia patients

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Abstract
Background: Recent studies have implicated variations in DNA methylation in the aetiology of schizophrenia. Genome-wide scans in both brain and blood report differential methylated regions (DMRs) and positions (DMPs) between patients with schizophrenia and healthy controls. Previously, we reported that DMRs where human specific methylation (hDMR) has occurred over evolutionary time are enriched for schizophrenia-associated markers (SCZ_hDMR). However, it is unknown whether these human specific DMRs show variable methylation in patients with schizophrenia.Methods: Using publicly available data, we investigate if human specific DMRs that harbour genetic variants associated with schizophrenia are differentially methylated between cases and controls.Results: We find statistically significant (p < 1e-4) methylation difference in schizophrenia associated human specific DMRs (SCZ hDMR) between brain samples of cases and controls. However, we fail to find evidence of similar differences in methylation in blood samples.Conclusion: Regions that are evolutionarily important for human species and that are associated with schizophrenia, also show difference in methylation variation in the brain in patients with schizophrenia.

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