Genetic Architecture of Major Depressive Disorder: From Heritability to Polygenic and Multi-Omics Insights

Major depressive disorder is a highly prevalent psychiatric disorder and a major contributor to global disability.While environmental factors such as stress and trauma play critical roles in its development, substantial evidence indicates a significant genetic component in individual susceptibility.Genetic research has progressed from family and twin studies to candidate gene approaches, genome-wide association studies (GWAS), and more recently integrative multiomics analyses.Heritability estimates suggest that depression is moderately heritable, typically ranging between 30% and 40%.However, identifying specific genetic determinants has been challenging due to the complex and highly polygenic nature of the disorder.Recent large-scale GWAS have identified multiple risk loci, supporting this polygenic architecture.In addition, environmental exposures may influence genetic risk through epigenetic mechanisms that regulate gene expression and neural plasticity.Integrative multi-omics approaches are providing new insights into the biological pathways underlying depression and may facilitate the development of precision psychiatry strategies.