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)
|
Text
167960.pdf - Published Version Available under License Creative Commons Attribution. 941kB |
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.
Item Type: | Articles |
---|---|
Status: | Published |
Refereed: | Yes |
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: | 1932-6203 |
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 |
University Staff: Request a correction | Enlighten Editors: Update this record