Genetic predictors of response to serotonergic and noradrenergic antidepressants in major depressive disorder: a genome-wide analysis of individual-level data and a meta-analysis.

<h4>Background</h4>It has been suggested that outcomes of antidepressant treatment for major depressive disorder could be significantly improved if treatment choice is informed by genetic data. This study aims to test the hypothesis that common genetic variants can predict response to an...

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Autores principales:	Katherine E Tansey, Michel Guipponi, Nader Perroud, Guido Bondolfi, Enrico Domenici, David Evans, Stephanie K Hall, Joanna Hauser, Neven Henigsberg, Xiaolan Hu, Borut Jerman, Wolfgang Maier, Ole Mors, Michael O'Donovan, Tim J Peters, Anna Placentino, Marcella Rietschel, Daniel Souery, Katherine J Aitchison, Ian Craig, Anne Farmer, Jens R Wendland, Alain Malafosse, Peter Holmans, Glyn Lewis, Cathryn M Lewis, Tine Bryan Stensbøl, Shitij Kapur, Peter McGuffin, Rudolf Uher
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/a911f831d0aa40feaf9412285f688221
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spelling	oai:doaj.org-article:a911f831d0aa40feaf9412285f6882212021-11-18T05:42:50ZGenetic predictors of response to serotonergic and noradrenergic antidepressants in major depressive disorder: a genome-wide analysis of individual-level data and a meta-analysis.1549-12771549-167610.1371/journal.pmed.1001326https://doaj.org/article/a911f831d0aa40feaf9412285f6882212012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23091423/pdf/?tool=EBIhttps://doaj.org/toc/1549-1277https://doaj.org/toc/1549-1676<h4>Background</h4>It has been suggested that outcomes of antidepressant treatment for major depressive disorder could be significantly improved if treatment choice is informed by genetic data. This study aims to test the hypothesis that common genetic variants can predict response to antidepressants in a clinically meaningful way.<h4>Methods and findings</h4>The NEWMEDS consortium, an academia-industry partnership, assembled a database of over 2,000 European-ancestry individuals with major depressive disorder, prospectively measured treatment outcomes with serotonin reuptake inhibiting or noradrenaline reuptake inhibiting antidepressants and available genetic samples from five studies (three randomized controlled trials, one part-randomized controlled trial, and one treatment cohort study). After quality control, a dataset of 1,790 individuals with high-quality genome-wide genotyping provided adequate power to test the hypotheses that antidepressant response or a clinically significant differential response to the two classes of antidepressants could be predicted from a single common genetic polymorphism. None of the more than half million genetic markers significantly predicted response to antidepressants overall, serotonin reuptake inhibitors, or noradrenaline reuptake inhibitors, or differential response to the two types of antidepressants (genome-wide significance p<5×10(-8)). No biological pathways were significantly overrepresented in the results. No significant associations (genome-wide significance p<5×10(-8)) were detected in a meta-analysis of NEWMEDS and another large sample (STARD), with 2,897 individuals in total. Polygenic scoring found no convergence among multiple associations in NEWMEDS and STARD.<h4>Conclusions</h4>No single common genetic variant was associated with antidepressant response at a clinically relevant level in a European-ancestry cohort. Effects specific to particular antidepressant drugs could not be investigated in the current study. Please see later in the article for the Editors' Summary.Katherine E TanseyMichel GuipponiNader PerroudGuido BondolfiEnrico DomeniciDavid EvansStephanie K HallJoanna HauserNeven HenigsbergXiaolan HuBorut JermanWolfgang MaierOle MorsMichael O'DonovanTim J PetersAnna PlacentinoMarcella RietschelDaniel SoueryKatherine J AitchisonIan CraigAnne FarmerJens R WendlandAlain MalafossePeter HolmansGlyn LewisCathryn M LewisTine Bryan StensbølShitij KapurPeter McGuffinRudolf UherPublic Library of Science (PLoS)articleMedicineRENPLoS Medicine, Vol 9, Iss 10, p e1001326 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Katherine E Tansey Michel Guipponi Nader Perroud Guido Bondolfi Enrico Domenici David Evans Stephanie K Hall Joanna Hauser Neven Henigsberg Xiaolan Hu Borut Jerman Wolfgang Maier Ole Mors Michael O'Donovan Tim J Peters Anna Placentino Marcella Rietschel Daniel Souery Katherine J Aitchison Ian Craig Anne Farmer Jens R Wendland Alain Malafosse Peter Holmans Glyn Lewis Cathryn M Lewis Tine Bryan Stensbøl Shitij Kapur Peter McGuffin Rudolf Uher Genetic predictors of response to serotonergic and noradrenergic antidepressants in major depressive disorder: a genome-wide analysis of individual-level data and a meta-analysis.
description	<h4>Background</h4>It has been suggested that outcomes of antidepressant treatment for major depressive disorder could be significantly improved if treatment choice is informed by genetic data. This study aims to test the hypothesis that common genetic variants can predict response to antidepressants in a clinically meaningful way.<h4>Methods and findings</h4>The NEWMEDS consortium, an academia-industry partnership, assembled a database of over 2,000 European-ancestry individuals with major depressive disorder, prospectively measured treatment outcomes with serotonin reuptake inhibiting or noradrenaline reuptake inhibiting antidepressants and available genetic samples from five studies (three randomized controlled trials, one part-randomized controlled trial, and one treatment cohort study). After quality control, a dataset of 1,790 individuals with high-quality genome-wide genotyping provided adequate power to test the hypotheses that antidepressant response or a clinically significant differential response to the two classes of antidepressants could be predicted from a single common genetic polymorphism. None of the more than half million genetic markers significantly predicted response to antidepressants overall, serotonin reuptake inhibitors, or noradrenaline reuptake inhibitors, or differential response to the two types of antidepressants (genome-wide significance p<5×10(-8)). No biological pathways were significantly overrepresented in the results. No significant associations (genome-wide significance p<5×10(-8)) were detected in a meta-analysis of NEWMEDS and another large sample (STARD), with 2,897 individuals in total. Polygenic scoring found no convergence among multiple associations in NEWMEDS and STARD.<h4>Conclusions</h4>No single common genetic variant was associated with antidepressant response at a clinically relevant level in a European-ancestry cohort. Effects specific to particular antidepressant drugs could not be investigated in the current study. Please see later in the article for the Editors' Summary.
format	article
author	Katherine E Tansey Michel Guipponi Nader Perroud Guido Bondolfi Enrico Domenici David Evans Stephanie K Hall Joanna Hauser Neven Henigsberg Xiaolan Hu Borut Jerman Wolfgang Maier Ole Mors Michael O'Donovan Tim J Peters Anna Placentino Marcella Rietschel Daniel Souery Katherine J Aitchison Ian Craig Anne Farmer Jens R Wendland Alain Malafosse Peter Holmans Glyn Lewis Cathryn M Lewis Tine Bryan Stensbøl Shitij Kapur Peter McGuffin Rudolf Uher
author_facet	Katherine E Tansey Michel Guipponi Nader Perroud Guido Bondolfi Enrico Domenici David Evans Stephanie K Hall Joanna Hauser Neven Henigsberg Xiaolan Hu Borut Jerman Wolfgang Maier Ole Mors Michael O'Donovan Tim J Peters Anna Placentino Marcella Rietschel Daniel Souery Katherine J Aitchison Ian Craig Anne Farmer Jens R Wendland Alain Malafosse Peter Holmans Glyn Lewis Cathryn M Lewis Tine Bryan Stensbøl Shitij Kapur Peter McGuffin Rudolf Uher
author_sort	Katherine E Tansey
title	Genetic predictors of response to serotonergic and noradrenergic antidepressants in major depressive disorder: a genome-wide analysis of individual-level data and a meta-analysis.
title_short	Genetic predictors of response to serotonergic and noradrenergic antidepressants in major depressive disorder: a genome-wide analysis of individual-level data and a meta-analysis.
title_full	Genetic predictors of response to serotonergic and noradrenergic antidepressants in major depressive disorder: a genome-wide analysis of individual-level data and a meta-analysis.
title_fullStr	Genetic predictors of response to serotonergic and noradrenergic antidepressants in major depressive disorder: a genome-wide analysis of individual-level data and a meta-analysis.
title_full_unstemmed	Genetic predictors of response to serotonergic and noradrenergic antidepressants in major depressive disorder: a genome-wide analysis of individual-level data and a meta-analysis.
title_sort	genetic predictors of response to serotonergic and noradrenergic antidepressants in major depressive disorder: a genome-wide analysis of individual-level data and a meta-analysis.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/a911f831d0aa40feaf9412285f688221
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Genetic predictors of response to serotonergic and noradrenergic antidepressants in major depressive disorder: a genome-wide analysis of individual-level data and a meta-analysis.

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