Polygenic risk scores for major depressive disorder and neuroticism as predictors of antidepressant response

Meta-analysis of three treatment cohorts

Joey Ward, Nicholas Graham, Rona J. Strawbridge, Amy Ferguson, Gregory Jenkins, Wenan Chen, Karen Hodgson, Mark A Frye, Richard M Weinshilboum, Rudolf Uher, Cathryn M. Lewis, Joanna M Biernacka, Daniel J. Smith

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

There are currently no reliable approaches for correctly identifying which patients with major depressive disorder (MDD) will respond well to antidepressant therapy. However, recent genetic advances suggest that Polygenic Risk Scores (PRS) could allow MDD patients to be stratified for antidepressant response. We used PRS for MDD and PRS for neuroticism as putative predictors of antidepressant response within three treatment cohorts: The Genome-based Therapeutic Drugs for Depression (GENDEP) cohort, and 2 sub-cohorts from the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomics Study PRGN-AMPS (total patient number = 760). Results across cohorts were combined via meta-analysis within a random effects model. Overall, PRS for MDD and neuroticism did not significantly predict antidepressant response but there was a consistent direction of effect, whereby greater genetic loading for both MDD (best MDD result, p < 5*10–5 MDD-PRS at 4 weeks, β = -0.019, S.E = 0.008, p = 0.01) and neuroticism (best neuroticism result, p < 0.1 neuroticism-PRS at 8 weeks, β = -0.017, S.E = 0.008, p = 0.03) were associated with less favourable response. We conclude that the PRS approach may offer some promise for treatment stratification in MDD and should now be assessed within larger clinical cohorts.

Original languageEnglish (US)
Article numbere0203896
JournalPLoS One
Volume13
Issue number9
DOIs
StatePublished - Sep 1 2018

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antidepressants
Major Depressive Disorder
meta-analysis
Antidepressive Agents
Meta-Analysis
pharmacogenomics
Therapeutics
therapeutics
Neuroticism
Pharmacogenetics
genetic improvement
drug therapy
Genes
drugs
Genome
Depression
genome
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Polygenic risk scores for major depressive disorder and neuroticism as predictors of antidepressant response : Meta-analysis of three treatment cohorts. / Ward, Joey; Graham, Nicholas; Strawbridge, Rona J.; Ferguson, Amy; Jenkins, Gregory; Chen, Wenan; Hodgson, Karen; Frye, Mark A; Weinshilboum, Richard M; Uher, Rudolf; Lewis, Cathryn M.; Biernacka, Joanna M; Smith, Daniel J.

In: PLoS One, Vol. 13, No. 9, e0203896, 01.09.2018.

Research output: Contribution to journalArticle

Ward, Joey ; Graham, Nicholas ; Strawbridge, Rona J. ; Ferguson, Amy ; Jenkins, Gregory ; Chen, Wenan ; Hodgson, Karen ; Frye, Mark A ; Weinshilboum, Richard M ; Uher, Rudolf ; Lewis, Cathryn M. ; Biernacka, Joanna M ; Smith, Daniel J. / Polygenic risk scores for major depressive disorder and neuroticism as predictors of antidepressant response : Meta-analysis of three treatment cohorts. In: PLoS One. 2018 ; Vol. 13, No. 9.
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