Please use this identifier to cite or link to this item: https://doi.org/10.1176/appi.ajp.2012.12020237
Title: Common genetic variation and antidepressant efficacy in major depressive disorder: A meta-analysis of three genome-wide pharmacogenetic studies
Authors: Uher, R.
Tansey, K.E.
Rietschel, M.
Henigsberg, N.
Maier, W.
Mors, O.
Hauser, J.
Placentino, A.
Souery, D.
Farmer, A.
Aitchison, K.J.
Craig, I.
McGuffin, P.
Lewis, C.M.
Ising, M.
Lucae, S.
Binder, E.B.
Kloiber, S.
Holsboer, F.
Müller-Myhsok, B.
Ripke, S.
Hamilton, S.P.
Soundy, J.
Laje, G.
McMahon, F.J.
Fava, M.
Rush, A.J. 
Perlis, R.H.
Issue Date: 1-Feb-2013
Citation: Uher, R., Tansey, K.E., Rietschel, M., Henigsberg, N., Maier, W., Mors, O., Hauser, J., Placentino, A., Souery, D., Farmer, A., Aitchison, K.J., Craig, I., McGuffin, P., Lewis, C.M., Ising, M., Lucae, S., Binder, E.B., Kloiber, S., Holsboer, F., Müller-Myhsok, B., Ripke, S., Hamilton, S.P., Soundy, J., Laje, G., McMahon, F.J., Fava, M., Rush, A.J., Perlis, R.H. (2013-02-01). Common genetic variation and antidepressant efficacy in major depressive disorder: A meta-analysis of three genome-wide pharmacogenetic studies. American Journal of Psychiatry 170 (2) : 207-217. ScholarBank@NUS Repository. https://doi.org/10.1176/appi.ajp.2012.12020237
Abstract: Objective: Indirect evidence suggests that common genetic variation contributes to individual differences in antidepressant efficacy among individuals with major depressive disorder, but previous studies may have been underpowered to detect these effects. Method: A meta-analysis was performed on data from three genome-wide pharma-cogenetic studies (the Genome-Based Therapeutic Drugs for Depression [GENDEP] project, the Munich Antidepressant Response Signature [MARS] project, and the Sequenced Treatment Alternatives to Relieve Depression [STAR*D] study), which included 2,256 individuals of Northern European descent with major depressive disorder, and antidepressant treatment outcomes were prospectively collected. After imputation, 1.2 million single-nucleotide polymorphisms were tested, capturing common variation for association with symptomatic improvement and remission after up to 12 weeks of antidepressant treatment. Results: No individual association met a genome-wide threshold for statistical significance in the primary analyses. A polygenic score derived from a meta-analysis of GENDEP and MARS participants accounted for up to approximately 1.2% of the variance in outcomes in STAR*D, suggesting a weakly concordant signal distributed over many polymorphisms. An analysis restricted to 1,354 individuals treated with citalopram (STAR*D) or escitalopram (GENDEP) identified an intergenic region on chromosome 5 associated with early improvement after 2 weeks of treatment. Conclusions: Despite increased statistical power accorded by meta-analysis, the authors identified no reliable predictors of antidepressant treatment outcome, although they did identify modest, direct evidence that common genetic variation contributes to individual differences in antidepressant response.
Source Title: American Journal of Psychiatry
URI: http://scholarbank.nus.edu.sg/handle/10635/109970
ISSN: 0002953X
DOI: 10.1176/appi.ajp.2012.12020237
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