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Uher, Rudolf; Perroud, Nader; Ng, Mandy Y M; Hauser, Joanna; Henigsberg, Neven; Maier, Wolfgang; Mors, Ole; Placentino, Anna; Rietschel, Marcella; Souery, Daniel; Zagar, 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
The American journal of psychiatry, 05/2010, Letnik: 167, Številka: 5Journal Article
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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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