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

• Published in: PloS one Vol. 13; no. 9; p. e0203896
• Main Authors: Ward, Joey, Graham, Nicholas, Strawbridge, Rona J, Ferguson, Amy, Jenkins, Gregory, Chen, Wenan, Hodgson, Karen, Frye, Mark, Weinshilboum, Richard, Uher, Rudolf, Lewis, Cathryn M, Biernacka, Joanna, Smith, Daniel J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.09.2018; Public Library of Science (PLoS)
• Subjects: Analysis; Antidepressants; Antidepressive Agents - therapeutic use; Biology and Life Sciences; Bipolar disorder; Cardiovascular disease; Cohort Studies; Consortia; Depression (Mood disorder); Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - genetics; Dosage and administration; Drug therapy; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Genomes; Humans; Male; Medicin och hälsovetenskap; Medicine and Health Sciences; Mental depression; Meta-analysis; Multifactorial Inheritance; Neurosis; Neuroticism; Neuroticism - drug effects; Patients; Pharmacogenomic Variants; Pharmacogenomics; Pharmacology; Physical Sciences; Polymorphism, Single Nucleotide; Principal Component Analysis; Psychiatry; Research and Analysis Methods; Risk Factors; Serotonin Uptake Inhibitors - therapeutic use; Studies; Glasgow Scotland; England; Scotland; United Kingdom > UK; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0203896

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.