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Type: Journal article
Title: Rare functional variants associated with antidepressant remission in Mexican-Americans: short title: antidepressant remission and pharmacogenetics in Mexican-Americans
Author: Wong, M.L.
Arcos-Burgos, M.
Liu, S.
Licinio, A.W.
Yu, C.
Chin, E.W.M.
Yao, W.D.
Lu, X.Y.
Bornstein, S.R.
Licinio, J.
Citation: Journal of Affective Disorders, 2021; 279:491-500
Publisher: Elsevier BV
Issue Date: 2021
ISSN: 0165-0327
Statement of
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
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: NCT00265291.
Keywords: Depression; pharmacogenomics; drug response; antidepressants; hispanic; whole-exome genotyping
Rights: © 2020 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (
DOI: 10.1016/j.jad.2020.10.027
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