Naslov
Genome-Wide Pharmacogenetics of Antidepressant Response in the GENDEP Project

Autori
Uher, Rudolf ; Perroud, Nader ; Ng Mandy Y. ; Hauser, Joanna ; Henigsberg, Neven ; Maier, Wolfgang ; Mors, Ole ; Placentino, Anna ; Rietschel, Marcella ; Souery, Daniel ; Žagar, Tina ; Czerski, Piotr M. ; Jerman, Borut ; Larsen, Erik Roj ; Schulze, Thomas G. ; Zobel, Astrid ; Cohen-Woods, Sarah ; Pirlo, Katrina ; Butler, Amy W. ; Muglia, Pierandrea ; Barnes, Michael R. ; Lathrop, Mark ; Farmer, Anne ; Breen, Gerome ; Aitchison, Katherine J. ; Craig, Ian ; Lewis, Cathryn M. ; McGuffin, Peter

Izvornik
American journal of psychiatry (0002-953X) 167 (2010), 5; 555-564

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
antidepressant response; GENDEP

Sažetak
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. 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. 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. 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.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA