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

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.

• Autores: Arcos Burgos, Oscar Mauricio; Wong, Ma Li; Liu, Sha; Licinio, Alice W.; Yu, Chenglong; Chin, Eunice W. M.; Yao, Wei Dong; Lu, Xin Yun; Bornstein, Stefan R.; Licinio, Julio
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2021
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/42122
• Acceso en línea: https://hdl.handle.net/10495/42122
• Palabra clave: Antidepressive Agents; Antidepresivos; Depressive Disorder, Major; Trastorno Depresivo Mayor; Double-Blind Method; Método Doble Ciego; Pharmacogenetics; Farmacogenética; Prospective Studies; Estudios Prospectivos; Treatment Outcome; Resultado del Tratamiento; Americanos Mexicanos; Mexican Americans; https://id.nlm.nih.gov/mesh/D000928; https://id.nlm.nih.gov/mesh/D003865; https://id.nlm.nih.gov/mesh/D004311; https://id.nlm.nih.gov/mesh/D010597; https://id.nlm.nih.gov/mesh/D011446; https://id.nlm.nih.gov/mesh/D016896; https://id.nlm.nih.gov/mesh/D017058
• Rights: openAccess
• License: http://creativecommons.org/licenses/by-nc-nd/2.5/co/