Genome-wide pharmacogenetics of antidepressant response in the GENDEP project.
Am J Psychiatry
; 167(5): 555-64, 2010 May.
Article
in En
| MEDLINE
| ID: mdl-20360315
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Depressive Disorder
/
Genome-Wide Association Study
/
Antidepressive Agents
Type of study:
Clinical_trials
/
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Am J Psychiatry
Year:
2010
Document type:
Article
Affiliation country:
United kingdom