The interplay of genetic background, epigenetics, and behavior: perspectives on the Iranian population

Abstract The intersection of genetics and epigenetics offers a profound framework for understanding complex behavioral phenotypes, including major depressive disorder (MDD), schizophrenia, addiction, and post-traumatic stress disorder (PTSD). While the global scientific community has mapped significant epigenetic markers associated with behavior, population-specific data remains crucial due to genetic heterogeneity. The Iranian population presents a unique genetic landscape characterized by high rates of consanguinity and distinct allelic frequencies in neuroregulatory genes such as BDNF, COMT, and 5-HTTLPR. This review synthesizes the interaction between this specific genetic background and epigenetic modifications triggered by environmental stressors such as war-related trauma providing a deeper understanding of the onset and heritability of these disorders. We highlight the potential role of homozygosity in amplifying epigenetic susceptibility and discuss the necessity for local “epigenome-wide association studies” (EWAS) to develop precision medicine (Nat Rev Genet 24(11):712–725, 2023, Methods Mol Biol 2745:187–212, 2024).