TY - JOUR
T1 - Polygenic risk scores for major depressive disorder and neuroticism as predictors of antidepressant response
T2 - Meta-analysis of three treatment cohorts
AU - Ward, Joey
AU - Graham, Nicholas
AU - Strawbridge, Rona J.
AU - Ferguson, Amy
AU - Jenkins, Gregory
AU - Chen, Wenan
AU - Hodgson, Karen
AU - Frye, Mark
AU - Weinshilboum, Richard
AU - Uher, Rudolf
AU - Lewis, Cathryn M.
AU - Biernacka, Joanna
AU - Smith, Daniel J.
N1 - Funding Information:
This work received support from Royal College of Physicians of Edinburgh JMAS Sims Fellowship, http://www.rcpe.ac.uk/college/jmas-sim-fellowship, UKRI Innovation- HDR-UK Fellowship (Grant MR/S003061/1 to Dr Rona J Strawbridge), MRC Doctoral Training Programme (Grant MR/K501335/1 to Ms Amy Ferguson), National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London to Prof Cathryn Lewis.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Disclaimer: This paper represents independent research part-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.
Publisher Copyright:
© 2018 Ward et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2018/9
Y1 - 2018/9
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0203896
DO - 10.1371/journal.pone.0203896
M3 - Article
C2 - 30240446
AN - SCOPUS:85054013350
SN - 1932-6203
VL - 13
JO - PLoS One
JF - PLoS One
IS - 9
M1 - e0203896
ER -