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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
Statement of
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
Antidepressive Agents
Antidepressive Agents, Second-Generation
Treatment Outcome
Oligonucleotide Array Sequence Analysis
Depressive Disorder
Depressive Disorder, Major
Psychiatric Status Rating Scales
Polymorphism, Single Nucleotide
Genome-Wide Association Study
Rights: Copyright © American Psychiatric Association
DOI: 10.1176/appi.ajp.2009.09070932
Appears in Collections:Aurora harvest
Psychiatry publications

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