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|Title:||Genome-wide pharmacogenetics of antidepressant response in the GENDEP project|
|Citation:||American Journal of Psychiatry, 2010; 167(5):555-564|
|Publisher:||Amer Psychiatric Press Inc|
|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|
|Appears in Collections:||Psychiatry publications|
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