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Recent Molecular Genetic Studies and Methodological Issues in Major Depression Research

Shih-Jen Tsai

    Major depressive disorder (MDD) is a genetically complex mental disorder involving numerous susceptible genes whose expression may be modulated by environmental factors. In the past decade, case-control association approaches have been the mainstream in MDD genetic studies. But whole genome gene-ex- pression microarray and genome-wide association studies have begun to emerge in recent years. Genetic association studies have suggested several genes related to MDD, although the results to date are inconclusive and no single genetic variation has been identified to increase the risk of depression substantially. Recent ap- proaches based on gene-environment interaction have demonstrated more consis- tent findings. Therefore, the usefulness from the study results of case-control stud- ies is limited by present knowledge of MDD pathophysiology. Genome-wide association studies are not constrained by our limited knowledge. Although the results of several recent genome-wide association studies did not reach the desired level of statistical significance, these studies do support interesting candidate genes and genomic regions for further study. In short, the field of genetic studies in gen- eral has been disappointing because to find common gene variants of large effect in MDD pathogenesis has been unsuccessful. However, the field of psychiatric genetics is rapidly growing, and several new technological advances (e.g.whole- genome sequencing) will be soon available for large-scale studies. These ap- proaches provide exciting new avenues to identify new candidate genes for MDD. A better understanding of the MDD-related genes may potentially lead to develop- ing effective prevention and treatment of this disease.
Key Word genetics, association study, genome-wide association study, epigenetics
Editorial Committe, Taiwanese Journal of Psychiatry
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