Abstract
Background: Pharmacogenetic studies aiming to personalize the treatment of depression are based on the assumption that response to antidepressants is a heritable trait, but there is no compelling evidence to support this. Methods: We estimate the contribution of common genetic variation to antidepressant response with Genome-Wide Complex Trait Analysis in a combined sample of 2799 antidepressant-treated subjects with major depressive disorder and genome-wide genotype data. Results: We find that common genetic variants explain 42% (SE =.180, p =.009) of individual differences in antidepressant response. Conclusions: These results suggest that response to antidepressants is a complex trait with substantial contribution from a large number of common genetic variants of small effect.
| Original language | English |
|---|---|
| Pages (from-to) | 679-682 |
| Number of pages | 4 |
| Journal | Biological Psychiatry |
| Volume | 73 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Apr 1 2013 |
Bibliographical note
Funding Information:We thank the National Institute of Mental Health (NIMH) for providing access to the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) genetic dataset. STAR*D was funded by NIMH via contract (N01MH90003) to the University of Texas Southwestern Medical Center at Dallas (A. John Rush, principal investigator). STAR*D genotyping was supported by an NIMH grant to SPH (Grant No. MH072802).
Funding Information:
The Novel Methods Leading to New Medications in Depression and Schizophrenia (NEWMEDS) project has been funded by the Innovative Medicine Initiative Joint Undertaking under grant agreement n° 115008, of which resources are composed of European Union and the European Federation of Pharmaceutical Industries and Associations (EFPIA) in-kind contribution and financial contribution from the European Union Seventh Framework Programme (FP7/2007-2013). The EFPIA members Pfizer, GlaxoSmithKline, and F. Hoffmann La-Roche have contributed work and samples to the project presented here. Genome-Based Therapeutic Drugs for Depression (GENDEP) was funded by the European Commission Framework 6 grant, EC Contract Ref.: LSHB-CT-2003-503428. Lundbeck provided nortriptyline and escitalopram for the GENDEP study. GlaxoSmithKline and the UK National Institute for Health Research of the Department of Health contributed to the funding of the sample collection at the Institute of Psychiatry, London. The GENDEP genotyping was funded by a joint grant from the U.K. Medical Research Council and GlaxoSmithKline (G0701420). Genetic and Clinical Predictors of Treatment Response in Depression (GenPod) was funded by the Medical Research Council (United Kingdom) and supported by the Mental Health Research Network. Geneva Outpatient Depression Study (GODS) study was partly supported by external funding provided by the Swiss branches of the following pharmaceutical companies: GlaxoSmithKline, Wyeth-Lederle, Bristol-Myers-Squibb, and Sanofi Aventis.
ASJC Scopus Subject Areas
- Biological Psychiatry