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Genetic predictors of response to serotonergic and noradrenergic antidepressants in major depressive disorder: a genome-wide analysis of individual-level data and a meta-analysis

Tansey, Katherine E., Guipponi, Michel, Perroud, Nader, Bondolfi, Guido, Domenici, Enrico, Evans, David, Hall, Stephanie K., Hauser, Joanna, Henigsberg, Neven, Hu, Xiaolan, Jerman, Borut, Maier, Wolfgang, Mors, Ole, O'Donovan, Michael Conlon, Peters, Tim J., Placentino, Anna, Rietschel, Marcella, Souery, Daniel, Aitchison, Katherine J., Craig, Ian, Farmer, Anne, Wendland, Jens R., Malafosse, Alain, Holmans, Peter Alan, Lewis, Glyn, Lewis, Cathryn M., Stensbøl, Tine Bryan, Kapur, Shitij, McGuffin, Peter and Uher, Rudolf 2012. Genetic predictors of response to serotonergic and noradrenergic antidepressants in major depressive disorder: a genome-wide analysis of individual-level data and a meta-analysis. Plos Medicine 9 (10) , e1001326. 10.1371/journal.pmed.1001326

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Abstract

Background It has been suggested that outcomes of antidepressant treatment for major depressive disorder could be significantly improved if treatment choice is informed by genetic data. This study aims to test the hypothesis that common genetic variants can predict response to antidepressants in a clinically meaningful way. Methods and Findings The NEWMEDS consortium, an academia–industry partnership, assembled a database of over 2,000 European-ancestry individuals with major depressive disorder, prospectively measured treatment outcomes with serotonin reuptake inhibiting or noradrenaline reuptake inhibiting antidepressants and available genetic samples from five studies (three randomized controlled trials, one part-randomized controlled trial, and one treatment cohort study). After quality control, a dataset of 1,790 individuals with high-quality genome-wide genotyping provided adequate power to test the hypotheses that antidepressant response or a clinically significant differential response to the two classes of antidepressants could be predicted from a single common genetic polymorphism. None of the more than half million genetic markers significantly predicted response to antidepressants overall, serotonin reuptake inhibitors, or noradrenaline reuptake inhibitors, or differential response to the two types of antidepressants (genome-wide significance p<5×10−8). No biological pathways were significantly overrepresented in the results. No significant associations (genome-wide significance p<5×10−8) were detected in a meta-analysis of NEWMEDS and another large sample (STAR*D), with 2,897 individuals in total. Polygenic scoring found no convergence among multiple associations in NEWMEDS and STAR*D. Conclusions No single common genetic variant was associated with antidepressant response at a clinically relevant level in a European-ancestry cohort. Effects specific to particular antidepressant drugs could not be investigated in the current study.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher: Public Library of Science
ISSN: 1549-1277
Date of First Compliant Deposit: 30 March 2016
Last Modified: 13 Apr 2019 02:55
URI: http://orca.cf.ac.uk/id/eprint/43110

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