Role of DNA Methylation in Mediating Genetic Risk of Psychiatric Disorders

Abstract

Psychiatric disorders are common, complex, and heritable conditions estimated to be the leading cause of disability worldwide. The last decade of research in genomics of psychiatry, performed by multinational, and multicenter collaborative efforts on hundreds of thousands of mental disorder cases and controls, provided invaluable insight into the genetic risk variants of these conditions. With increasing cohort sizes, more risk variants are predicted to be identified in the near future, but there appears to be a knowledge gap in understanding how these variants contribute to the pathophysiology of psychiatric disorders. Majority of the identified common risk single-nucleotide polymorphisms (SNPs) are non-coding but are enriched in regulatory regions of the genome. It is therefore of great interest to study the impact of identified psychiatric disorders' risk SNPs on DNA methylation, the best studied epigenetic modification, playing a pivotal role in the regulation of transcriptomic processes, brain development, and functioning. This work outlines the mechanisms through which risk SNPs can impact DNA methylation levels and provides a summary of current evidence on the role of DNA methylation in mediating the genetic risk of psychiatric disorders.