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Am J Psychiatry. 2010 May;167(5):555-64. doi: 10.1176/appi.ajp.2009.09070932. Epub 2010 Apr 1.

Genome-wide pharmacogenetics of antidepressant response in the GENDEP project.

Author information

  • 1Medical Research Council Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, SE5 8AF, London, United Kingdom. rudolf.uher@iop.kcl.ac.uk

Abstract

OBJECTIVE:

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.

METHOD:

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.

RESULTS:

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.

CONCLUSIONS:

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.

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PMID:
20360315
[PubMed - indexed for MEDLINE]
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