T171. High Polygenic Burden Is Associated With Blood Dna Methylation Changes in Individuals With Suicidal Behavior

Abstract

Background Suicidal behavior may be divided into completed suicide, suicide attempts, and suicidal ideation. It has been suggested that these behaviors represent a continuum and result from the interaction of several contributors, including genetic and environmental factors. The integration of approaches considering the polygenic component of suicidal behavior, such as polygenic risk scores (PRS) and DNA methylation is promising for improving our understanding of the complex interplay between genetic and environmental factors in this behavior. The aim of this study was the evaluation of DNA methylation differences between individuals with high and low genetic burden for suicidality. Methods The present study was divided into two phases. In the first phase, genotyping with the Psycharray chip was performed in a discovery sample of 568 Mexican individuals, of which 149 had suicidal behavior (64 individuals with suicidal ideation, 50 with suicide attempt and 35 with completed suicide) and 419 non-suicide controls. Then, a PRS analysis based on summary statistics from the Psychiatric Genomic Consortium was performed in the discovery sample. In a second phase, we evaluated DNA methylation differences between individuals with high and low genetic burden for suicidality in a sub-sample of the discovery sample (target sample) of 94 subjects. Methylation profile from individuals in the target sample was assessed with the Illumina Infinium Human Methylation EPIC BeadChip. Results We identified 153 differentially methylated sites between individuals with low and high-PRS. From these, 91 sites were hypermethylated and 62 hypomethylated in the high PRS group relative to low PRS group. Among genes mapped to differentially methylated sites, we found genes involved in neurodevelopment and ATP binding. Discussion To our knowledge, this is the first study integrating polygenic risk scores and DNA methylation in suicidality. Our results suggest that genetic variants might increase the predisposition to epigenetic variations in genes involved in neurodevelopment. This study highlights the possible implication of polygenic burden in the alteration of epigenetic changes in suicidal behavior.