Abstract
Introduction: Rare genetic functional variants can contribute to 30-40% of functional variability in genes relevant to drug action. Therefore, we investigated the role of rare functional variants in antidepressant response. Method: Mexican-American individuals meeting the Diagnostic and Statistical Manual-IV criteria for major depressive disorder (MDD) participated in a prospective randomized, double-blind study with desipramine or fluoxetine. The rare variant analysis was performed using whole-exome genotyping data. Network and pathway analyses were carried out with the list of significant genes. Results: The Kernel-Based Adaptive Cluster method identified functional rare variants in 35 genes significantly associated with treatment remission (False discovery rate, FDR <0.01). Pathway analysis of these genes supports the involvement of the following gene ontology processes: olfactory/sensory transduction, regulation of response to cytokine stimulus, and meiotic cell cycleprocess. Limitations: Our study did not have a placebo arm. We were not able to use antidepressant blood level as a covariate. Our study is based on a small sample size of only 65 Mexican-American individuals. Further studies using larger cohorts are warranted. Conclusion: Our data identified several rare functional variants in antidepressant drug response in MDD patients. These have the potential to serve as genetic markers for predicting drug response. Trial registration: ClinicalTrials.gov
Original language | English (US) |
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Pages (from-to) | 491-500 |
Number of pages | 10 |
Journal | Journal of Affective Disorders |
Volume | 279 |
DOIs | |
State | Published - Jan 15 2021 |
Keywords
- Antidepressants
- Depression
- Drug response
- Hispanic
- Pharmacogenomics
- Whole-exome genotyping
ASJC Scopus subject areas
- Clinical Psychology
- Psychiatry and Mental health