Hypomethylation of LINE-1 elements in schizophrenia and bipolar disorder

Schizophrenia (SCZ) and bipolar disorder (BPD) are severe mental illnesses with evidence of significant genetic and environmental etiological elements in their complex etiologies. 5'-Methylcytosine is the main epigenetic DNA modification that mediates the interplay between genetic and environmental components. In humans, most 5'-methylcytosine modifications are observed in CpG-rich regions within the long interspersed nuclear element (LINE-1). LINE-1 is a mobile retrotransposon that comprises ∼17% of the human genome, and its methylation levels are highly correlated with global DNA methylation levels. LINE-1 insertions are also reported to be mental illnesses-associated genomic risk factors. To examine the LINE-1 methylation levels in SCZ and BPD, this study employed a bisulfite conversion-specific one-label extension (BS-OLE) method to detect the methylation levels at three CpG sites (S1, S2 and S3) of LINE-1 in peripheral blood DNA from a Han Chinese cohort composed of 92 SCZ patients, 99 BPD patients and 92 controls (CON). The results showed a decreased S1 methylation level in SCZ, decreased S2 methylation level in BPD and decreased S3 methylation levels in both SCZ and BPD relative to those of the CON. A female-dependent positive correlation of the S3 methylation level with age in CON became non-significant in both SCZ and BPD. These findings demonstrated that LINE-1 methylation varied with development and disease status. The roles of LINE-1 methylation in the pathogenesis of SCZ and BPD remain to be elucidated.