Genome-wide DNA methylation in suicide victims revealing impact on gene expression

Abstract

BackgroundSuicidal behavior is a multifactorial, polygenic state that affects millions worldwide. It is a result of interplay between hereditary and environmental factors, tied together by epigenetics. Despite vast knowledge on suicidality complete mechanism and factors leading to suicide are unknown. However there is an indication between changes in DNA methylation patterns and suicidal behavior. MethodsTo identify differential methylation we formed a homogenous group of male suicide victims who died by hanging and control group. Altogether our study included 18 subjects in which two brain regions, Brodmann area 9 (9 suicide victims and 9 controls)) and hippocampus (6 suicide victims and 6 controls) were investigated using next-generation sequencing (NGS). ResultsOur results have shown several differences in methylation level between suicide victims and controls in both brain regions (>25% difference in methylation and q-value < 0.01), with gene ontology pointing towards cell structural integrity and nervous system regulation. Additional gene expression analysis identified changes in two genes, ZNF714 (p-value = 0.002) and NRIP3 (p-value = 0.046). LimitationsMajor limitation is small sample size. Our analysis was conducted on brain tissue including different cell types so the results are a representation of a methylation pattern for the whole brain tissue sample. ConclusionsWe performed a preliminary methylation study with single base pair resolution using NGS on one of the world populations with a very high suicide risk. Obtained results offer novel insights into altered methylation patterns in suicide victims, which could provide a starting point for further studies on clinical samples with highly expressed suicide risk.