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Pharmacogenetics of antidepressant response: a polygenic approach

García-González, Judit, Tansey, Katherine E., Hauser, Joanna, Henigsberg, Neven, Maier, Wolfgang, Mors, Ole, Placentino, Anna, Rietschel, Marcella, Souery, Daniel, Zagar, Tina, Czerski, Piotr M., Jerman, Borut, Buttenschøn, Henriette N., Schulze, Thomas G., Zobel, Astrid, Farmer, Anne, Aitchison, Katherine J., Craig, Ian, McGuffin, Peter, Giupponi, Michel, Perroud, Nader, Bondolfi, Guido, Evans, David, O'Donovan, Michael Conlon ORCID:, Peters, Tim J., Wendland, Jens R., Lewis, Glyn, Kapur, Shitij, Perlis, Roy, Arolt, Volker, Domschke, Katharina, Breen, Gerome, Curtis, Charles, Sang-Hyuk, Lee, Kan, Carol, Newhouse, Stephen, Patel, Hamel, Baune, Bernhard T., Uher, Rudolf, Lewis, Cathryn M. and Fabbri, Chiara 2017. Pharmacogenetics of antidepressant response: a polygenic approach. Progress in Neuro-Psychopharmacology and Biological Psychiatry 75 , pp. 128-134. 10.1016/j.pnpbp.2017.01.011

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Background Major depressive disorder (MDD) has a high personal and socio-economic burden and > 60% of patients fail to achieve remission with the first antidepressant. The biological mechanisms behind antidepressant response are only partially known but genetic factors play a relevant role. A combined predictor across genetic variants may be useful to investigate this complex trait. Methods Polygenic risk scores (PRS) were used to estimate multi-allelic contribution to: 1) antidepressant efficacy; 2) its overlap with MDD and schizophrenia. We constructed PRS and tested whether these predicted symptom improvement or remission from the GENDEP study (n = 736) to the STAR*D study (n = 1409) and vice-versa, including the whole sample or only patients treated with escitalopram or citalopram. Using summary statistics from Psychiatric Genomics Consortium for MDD and schizophrenia, we tested whether PRS from these disorders predicted symptom improvement in GENDEP, STAR*D, and five further studies (n = 3756). Results No significant prediction of antidepressant efficacy was obtained from PRS in GENDEP/STAR*D but this analysis might have been underpowered. There was no evidence of overlap in the genetics of antidepressant response with either MDD or schizophrenia, either in individual studies or a meta-analysis. Stratifying by antidepressant did not alter the results. Discussion We identified no significant predictive effect using PRS between pharmacogenetic studies. The genetic liability to MDD or schizophrenia did not predict response to antidepressants, suggesting differences between the genetic component of depression and treatment response. Larger or more homogeneous studies will be necessary to obtain a polygenic predictor of antidepressant response.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Elsevier
ISSN: 0278-5846
Date of First Compliant Deposit: 27 February 2018
Date of Acceptance: 26 January 2017
Last Modified: 06 Nov 2023 17:43

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