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. Please see later in the article for the Editors' Summary. Tansey et al.
| Original language | English |
|---|---|
| Article number | e1001326 |
| Journal | PLoS Medicine |
| Volume | 9 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Oct 2012 |
Bibliographical note
Funding Information:GB is a member of a national advisory board for Bristol-Myer Squibb and Pfizer and has received research funding from GlaxoSmithKline, Wyeth-Lederle, Bristol-Myers-Squibb, and Sanofi Aventis. ED and JRW are full-time employees of Roche. ED was a full time employee of GlaxoSmithKline when he undertook work on this study. SKH and XH are full-time employees of Pfizer. NH has participated in clinical trials sponsored by pharmaceutical companies including GlaxoSmithKline and Lundbeck and received honoraria for participating in expert panels from pharmaceutical companies including Lundbeck. MO’D's department received £2000 in lieu of an honorarium to MO'D from Lilly as a result of his participation in sponsored symposia in 2012. Those symposia were unrelated to the contents of this manuscript. MO’D holds grants from the Medical Research Council (UK), The Wellcome Trust, the National Institutes of Medicine (USA), and the European Union. None are relevant to the contents of this manuscript. DS is a member of a national advisory boards for Astra-Zeneca, Bristol-Myers Squibb, Eli Lilly, and Lundbeck. KJA is a member of a national advisory board for Johnson & Johnson, Lundbeck, Roche Diagnostics, and Bristol-Myers Squibb and Otsuka Pharmaceuticals Limited and has received consultancy fees and honoraria from Bristol-Myers Squibb, Lundbeck, Roche Molecular Systems, Roche Diagnostics, and Johnson & Johnson. KJA has received research and development consultancy fees and research support from Roche Diagnostics and Roche Molecular Systems. KJA has received research grants from Bristol-Myers Squibb and Otsuka Pharmaceuticals Limited; Johnson & Johnson Pharmaceutical Research and Development. PM and AF have previously received consultancy fees and honoraria for participating in expert panels from pharmaceutical companies including Lundbeck and GlaxoSmithKline, but have had no such income in the last 3 years. CML is on the Editorial Board of PLOS Medicine. TBS is a full time employee of Lundbeck. SK has received research funding from AstraZeneca, Bristol-Myers Squibb, and GlaxoSmithKline, and has served as consultant and/or speaker for AstraZeneca, Bioline, BMS-Otsuka, Eli Lilly, Janssen, Lundbeck, NeuroSearch, Pfizer, Roche, Servier, and Solvay Wyeth. All other authors have declared that no competing interests exist.
ASJC Scopus Subject Areas
- General Medicine