Past Issues
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 |
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