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.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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 (STAR*D), with 2,897 individuals in total. Polygenic scoring found no convergence among multiple associations in NEWMEDS and STAR*D.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Psychiatry, King's College London, London, UK.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Tansey
authors.forename: Michel
authors.initials: M
authors.lastname: Guipponi
authors.forename: Nader
authors.initials: N
authors.lastname: Perroud
authors.forename: Guido
authors.initials: G
authors.lastname: Bondolfi
authors.forename: Enrico
authors.initials: E
authors.lastname: Domenici
authors.forename: David
authors.initials: D
authors.lastname: Evans
authors.forename: Stephanie K
authors.initials: SK
authors.lastname: Hall
authors.forename: Joanna
authors.initials: J
authors.lastname: Hauser
authors.forename: Neven
authors.initials: N
authors.lastname: Henigsberg
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Hu
authors.forename: Borut
authors.initials: B
authors.lastname: Jerman
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.forename: Ole
authors.initials: O
authors.lastname: Mors
authors.forename: Michael
authors.initials: M
authors.lastname: O'Donovan
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Peters
authors.forename: Anna
authors.initials: A
authors.lastname: Placentino
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Daniel
authors.initials: D
authors.lastname: Souery
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Aitchison
authors.forename: Ian
authors.initials: I
authors.lastname: Craig
authors.forename: Anne
authors.initials: A
authors.lastname: Farmer
authors.forename: Jens R
authors.initials: JR
authors.lastname: Wendland
authors.forename: Alain
authors.initials: A
authors.lastname: Malafosse
authors.forename: Peter
authors.initials: P
authors.lastname: Holmans
authors.forename: Glyn
authors.initials: G
authors.lastname: Lewis
authors.forename: Cathryn M
authors.initials: CM
authors.lastname: Lewis
authors.forename: Tine Bryan
authors.initials: TB
authors.lastname: Stensbøl
authors.forename: Shitij
authors.initials: S
authors.lastname: Kapur
authors.forename: Peter
authors.initials: P
authors.lastname: McGuffin
authors.forename: Rudolf
authors.initials: R
authors.lastname: Uher
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D017367:Selective Serotonin Reuptake Inhibitors