Polygenic risk scores for major depressive disorder and neuroticism as predictors of antidepressant response: meta-analysis of three treatment cohorts

Ward, J. et al. (2018) Polygenic risk scores for major depressive disorder and neuroticism as predictors of antidepressant response: meta-analysis of three treatment cohorts. PLoS ONE, 13(9), e0203896. (doi: 10.1371/journal.pone.0203896) (PMID:30240446) (PMCID:PMC6150505)

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Smith, Professor Daniel and Graham, Dr Nicholas and Ward, Dr Joey and Ferguson, Amy and Strawbridge, Dr Rona
Creator Roles:
Ward, J.Conceptualization, Investigation, Methodology, Writing – original draft, Writing – review and editing
Graham, N.Methodology, Writing – review and editing
Strawbridge, R. J.Methodology, Writing – review and editing
Ferguson, A.Methodology, Writing – review and editing
Smith, D. J.Conceptualization, Data curation, Methodology, Resources, Writing – review and editing
Authors: Ward, J., Graham, N., Strawbridge, R. J., Ferguson, A., Jenkins, G., Chen, W., Hodgson, K., Frye, M., Weinshilboum, R., Uher, R., Lewis, C. M., Biernacka, J., and Smith, D. J.
College/School:College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN (Online):1932-6203
Copyright Holders:Copyright © 2018 Ward et al.
First Published:First published in PLoS ONE 13(9): e0203896
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
632341MRC Doctoral Training Grant 2013/14, 2014/15 and 2015/16George BaillieMedical Research Council (MRC)MR/K501335/1MVLS GRADUATE SCHOOL