Format

Send to

Choose Destination
PLoS One. 2018 Sep 21;13(9):e0203896. doi: 10.1371/journal.pone.0203896. eCollection 2018.

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

Author information

1
Institute of Health And Wellbeing, University of Glasgow, Glasgow, Scotland.
2
Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
3
Mayo Clinic, Rochester, MN, United States of America.
4
St. Jude Children's Research Hospital, Memphis, TN, United States of America.
5
King's College London, London, England.
6
Dalhousie University, Halifax, Canada.

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.

PMID:
30240446
PMCID:
PMC6150505
DOI:
10.1371/journal.pone.0203896
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center