Side Effects and Genetic Variation During Depression in Taiwanese Han Population

Abstract

Genetic variation can play a role in individual differences in the response to medications used for the treatment of depression, as well as in the occurrence of side effects. While there have been studies investigating genetic factors associated with antidepressant response and side effects, it is important to note that the field of pharmacogenetics is complex and influenced by multiple genetic and environmental factors. In the case of the Taiwanese Han population and depression, limited specific studies examining the relationship between genetic variation and antidepressant response or side effects have been conducted.  Huang and colleagues analyzed the syndromal factor structures of the Hamilton Depression Rating Scale in 479 patients with MDD by using exploratory factor analysis. All patients were followed up biweekly for 8 weeks. In total, 33 independent SNPs for treatment responses were tested in a mixed model, 12 of which demonstrated a p value <0.05. The most significant SNP was rs2182717 in the ENSR00000803469 gene located on chromosome 6 for the core syndromal factor (β = -0.638, p = 1.8 × 10^-4) in terms of symptom improvement over time. Patients with a GG or GA genotype with the rs2182717 SNP also exhibited a treatment response (β = 0.089, p = 2.0 × 10^-6) at week 4. Moreover, rs1836075352 was associated with sexual side effects (p = 3.2 × 10^-8). Pathway and network analyses using the identified SNPs revealed potential biological functions involved in treatment response, such as neurodevelopment-related functions and immune processes. In conclusion, they identified loci that may affect the clinical response to treatment with antidepressants in the context of empirically defined depressive syndromal factors and side effects among the Taiwanese Han population, thus providing novel biological targets for further investigation. Pharmacogenomics J. 2023 May;23(2-3):50-59.  doi: 10.1038/s41397-023-00298-8.