Chapter 3 - Gene-Environment Interactions and Epigenetic Mechanisms in Depression

Abstract

Major depressive disorder (MDD) is a debilitating disorder of a complex nature with multiple risk factors contributing to its etiology. Candidate gene and genome-wide association studies (GWAS) partially explain the variance in pathology, indicating that environmental factors such as childhood maltreatment (CM) and stressful life events (SLEs) also play a key role in the etiology of MDD. Therefore, a thorough understanding of the current knowledge on gene-environmental (G×E) interaction effects in the prediction of MDD is valuable in terms of early and better intervention in those with increased genetic or environmental risks. In this chapter, we review current evidence of effects of G×E on MDD and epigenetics mechanisms mediating these effects. The review suggests that although high-risk polymorphisms such as the serotonin transporter variant and the brain-derived neurotrophic factor variants are critical in the pathology, the interactions are not replicated consistently. In contrast, genome-wide G×E analysis using polygenic risk scores for MDD lacks the sample size and standardized environmental assessment tools. Genome-wide G×E prioritizing biological effects using epigenomics and transcriptomics data along with the environmental effect is an important future topic of research.