Rare Functional Variants Associated with Antidepressant Remission in Mexican-Americans: Short title: Antidepressant remission and pharmacogenetics in Mexican-Americans

Ma Li Wong, Mauricio Arcos-Burgos, Sha Liu, Alice W. Licinio, Chenglong Yu, Eunice W.M. Chin, Wei Dong Yao, Xin Yun Lu, Stefan R. Bornstein, Julio Licinio

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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 NCT00265291

Original languageEnglish (US)
Pages (from-to)491-500
Number of pages10
JournalJournal of Affective Disorders
Volume279
DOIs
StatePublished - Jan 15 2021

Keywords

  • Antidepressants
  • Depression
  • Drug response
  • Hispanic
  • Pharmacogenomics
  • Whole-exome genotyping

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health

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