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https://hdl.handle.net/2440/76296
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Type: | Journal article |
Title: | Genome-wide pharmacogenetics of antidepressant response in the GENDEP project |
Author: | Uher, R. Perroud, N. Ng, M. Hauser, J. Henigsberg, N. Maier, W. Mors, O. Placentino, A. Rietschel, M. Souery, D. Zagar, T. Czerski, P. Jerman, B. Larsen, E. Schulze, T. Zobel, A. Cohen-Woods, S. Pirlo, K. Butler, A. Muglia, P. et al. |
Citation: | American Journal of Psychiatry, 2010; 167(5):555-564 |
Publisher: | Amer Psychiatric Press Inc |
Issue Date: | 2010 |
ISSN: | 0002-953X 1535-7228 |
Statement of Responsibility: | Rudolf Uher... Sarah Cohen-Woods... et al. |
Abstract: | <h4>Objective</h4>The purpose of this study was to identify genetic variants underlying the considerable individual differences in response to antidepressant treatment. The authors performed a genome-wide association analysis of improvement of depression severity with two antidepressant drugs.<h4>Method</h4>High-quality Illumina Human610-quad chip genotyping data were available for 706 unrelated participants of European ancestry treated for major depression with escitalopram (N=394) or nortriptyline (N=312) over a 12-week period in the Genome-Based Therapeutic Drugs for Depression (GENDEP) project, a partially randomized open-label pharmacogenetic trial.<h4>Results</h4>Single nucleotide polymorphisms in two intergenic regions containing copy number variants on chromosomes 1 and 10 were associated with the outcome of treatment with escitalopram or nortriptyline at suggestive levels of significance and with a high posterior likelihood of true association. Drug-specific analyses revealed a genome-wide significant association between marker rs2500535 in the uronyl 2-sulphotransferase gene and response to nortriptyline. Response to escitalopram was best predicted by a marker in the interleukin-11 (IL11) gene. A set of 72 a priori-selected candidate genes did not show pharmacogenetic associations above a chance level, but an association with response to escitalopram was detected in the interleukin-6 gene, which is a close homologue of IL11.<h4>Conclusions</h4>While limited statistical power means that a number of true associations may have been missed, these results suggest that efficacy of antidepressants may be predicted by genetic markers other than traditional candidates. Genome-wide studies, if properly replicated, may thus be important steps in the elucidation of the genetic basis of pharmacological response. |
Keywords: | Humans Citalopram Nortriptyline Sulfotransferases Antidepressive Agents Antidepressive Agents, Second-Generation Interleukin-6 Interleukin-11 Treatment Outcome Oligonucleotide Array Sequence Analysis Depressive Disorder Depressive Disorder, Major Psychiatric Status Rating Scales Pharmacogenetics Genotype Phenotype Polymorphism, Single Nucleotide Genome-Wide Association Study |
Rights: | Copyright © American Psychiatric Association |
DOI: | 10.1176/appi.ajp.2009.09070932 |
Published version: | http://dx.doi.org/10.1176/appi.ajp.2009.09070932 |
Appears in Collections: | Aurora harvest Psychiatry publications |
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