The association of DNA methylation and brain volume in healthy individuals and schizophrenia patients

Abstract

Both methylation and brain volume patterns hold important biological information for the development and prognosis of schizophrenia (SZ). A combined study to probe the association between them provides a new perspective to understanding SZ. Genomic methylation of peripheral blood and regional brain volumes derived from magnate resonance imaging were analyzed using parallel independent component analyses in this study. Nine methylation components and five brain volumetric components were extracted for 94 SZ patients and 106 healthy controls. After controlling for age, sex, race, and substance use, a component comprised primarily of bilateral cerebellar volumes was significantly correlated to a methylation component from 14 CpG sites in 13 genes. Both patients and healthy controls demonstrated similar associations, but patients had significantly smaller cerebellar volumes and dysmethylation in the associated epigenetic component compared to controls. The 13 genes are enriched in cellular growth and proliferation with some genes involved in neuronal growth and cerebellum development (GATA4, ADRA1D, EPHA3, and KCNK10), and these genes are prominently associated with neurological and psychological disorders. Such findings suggest that the methylation pattern of the genes coding for cellular growth may influence the cerebellar development through regulating gene expression, and the alteration in the methylation of these genes in SZ patients may contribute to the cerebellar volume reduction observed in patients.

The role of DNA methylation in the pathophysiology and treatment of bipolar disorder

“…Specifically, Horvarth et al was able to find a correlation of around r = 0.9 across the 2 tissues (Horvath et al, 2012), and DNA methylation changes in ten genes identified in the brain of schizophrenic and BD patients have also been confirmed in peripheral blood samples (Xiao et al, 2014). In addition, methylation in peripheral blood has been correlated with brain volume in healthy individuals and schizophrenia patients (Liu et al, 2015), and it has also been correlated with symptoms of major psychiatric disorders, including schizophrenia, depression and BD (Liu et al, 2014; Sabunciyan et al, 2015). …”

Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group

“…Crucially, while initial reports have demonstrated that although DNA methylation patterns are largely tissue-specific, often differing between blood and brain [20,21], there are also similarities [22] and blood DNA methylation shows promise as a biomarker for brain-related traits, including neuropsychiatric disorders [23][24][25][26][27], cognitive ability [28,29] and future psychopathology [26]. However, only a few studies of small sample sizes have reported associations between blood DNA methylation and brain phenotypes [26,[30][31][32].…”

Rare variants in drug target genes contributing to complex diseases, phenome-wide

“…We identified 2120 such associations from the ICD-9 analyses and 31 associations from the clinical lab analyses where the results are filtered at P-value of 0.001. Among the most significant associations is a novel association between the gene PTGS2 (Prostaglandin-Endoperoxide Synthase 2) and ICD-9 493.20 (chronic obstructive asthma) with P-value = 4.90e − 08 and also between the gene ADRA1D and ICD9-9 780.93 (memory loss) with P-value = 7.64e − 07, where the gene ADRA1D is already known to be associated with Schizophrenia 47 . All Bonferroni significant results in this category are shown in Supplementary Table 1 .…”