International Journal of Molecular Medical Science, 2024, Vol.14, No.4, 216-226 http://medscipublisher.com/index.php/ijmms 217 2019). Such approaches have shown promise in improving response and remission rates in patients with difficult-to-treat depression (Greden et al., 2019). This study aims to review the current state of genomic research in the context of depression and explore its implications for personalized treatment. By synthesizing findings from recent genomic studies, this review aims to provide a comprehensive overview of the genetic architecture of depression and discuss how these insights can be translated into clinical practice to enhance treatment efficacy. The ultimate goal is to highlight the potential of genomics to revolutionize the management of depression, offering hope for more effective and individualized therapeutic strategies. 2 Genomic Factors in Depression 2.1 Genetic variants associated with depression Genome-wide association studies (GWAS) have significantly advanced our understanding of the genetic underpinnings of major depressive disorder (MDD). Recent meta-analyses combining data from multiple large-scale studies have identified several genetic loci associated with MDD. For instance, a meta-analysis involving 90 150 MDD cases and 246 603 controls identified significant associations at loci 6q16.2, 12q24.31, and 16p13.3, suggesting that genetic variants at these loci may confer risk for MDD through the regulation of gene expression in brain tissues (Li et al., 2018). Another study identified 15 genetic loci associated with MDD in individuals of European descent, highlighting the potential of large-scale consumer genomic data to complement traditional research methods (Hyde et al., 2016). These findings underscore the polygenic nature of depression, where multiple genetic variants each contribute a small effect to the overall risk (Cohen-Woods et al., 2012; Shadrina et al., 2018). Specific genes and loci have been implicated in the risk for depression through GWAS. For example, the FBXL4 and RSRC1 genes located at the 16p13.3 locus were found to be significantly upregulated in the brains of MDD patients, suggesting their involvement in the pathogenesis of depression (Alladi et al., 2018). Additionally, the HACE1 and SHANK2 genes have been implicated through studies examining the interplay between genetic variants and DNA methylation. Lower DNA methylation at the HACE1 promoter was associated with higher risk for depression, while SHANK2 was linked to neuronal processes through miRNA regulation (Ciuculete et al., 2020). These findings provide insights into the molecular mechanisms underlying depression and highlight potential targets for therapeutic intervention. 2.2 Epigenetic factors Epigenetic modifications, such as DNA methylation and histone modification, play a crucial role in the regulation of gene expression and have been implicated in the pathophysiology of depression. DNA methylation, in particular, has been extensively studied as a potential biomarker for depression. For instance, a meta-analysis of epigenome-wide association studies (EWAS) identified three CpG sites significantly associated with depressive symptoms, pointing towards axon guidance as a disrupted pathway in depression (Jovanova et al., 2018). Histone modifications, although less studied in the context of depression, are known to influence chromatin structure and gene expression, potentially contributing to the development of depressive disorders (Shadrina et al., 2018). Environmental factors, such as stress and trauma, can induce epigenetic changes that influence the risk of developing depression. Twin studies have shown that monozygotic twins discordant for depression exhibit differences in DNA methylation, suggesting that environmental factors contribute to these epigenetic modifications (Alladi et al., 2018). Additionally, childhood trauma has been linked to alterations in DNA methylation patterns, which may predispose individuals to depression later in life (Li et al., 2018). These findings highlight the importance of considering both genetic and environmental factors in understanding the etiology of depression. 2.3 Gene-environment interactions The interaction between genetic predisposition and environmental stressors is a critical factor in the development of depression. Studies have shown that individuals with certain genetic variants are more susceptible to the effects
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