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

Author

Listed:
  • Joey Ward
  • Nicholas Graham
  • Rona J Strawbridge
  • Amy Ferguson
  • Gregory Jenkins
  • Wenan Chen
  • Karen Hodgson
  • Mark Frye
  • Richard Weinshilboum
  • Rudolf Uher
  • Cathryn M Lewis
  • Joanna Biernacka
  • Daniel J Smith

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

Suggested Citation

  • Joey Ward & Nicholas Graham & Rona J Strawbridge & Amy Ferguson & Gregory Jenkins & Wenan Chen & Karen Hodgson & Mark Frye & Richard Weinshilboum & Rudolf Uher & Cathryn M Lewis & Joanna Biernacka & D, 2018. "Polygenic risk scores for major depressive disorder and neuroticism as predictors of antidepressant response: Meta-analysis of three treatment cohorts," PLOS ONE, Public Library of Science, vol. 13(9), pages 1-8, September.
    • Handle: RePEc:plo:pone00:0203896
    DOI: 10.1371/journal.pone.0203896
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    References listed on IDEAS

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    1. Frank Dudbridge, 2013. "Power and Predictive Accuracy of Polygenic Risk Scores," PLOS Genetics, Public Library of Science, vol. 9(3), pages 1-17, March.
    2. Viechtbauer, Wolfgang, 2010. "Conducting Meta-Analyses in R with the metafor Package," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 36(i03).
    3. David M. Howard & Mark J. Adams & Masoud Shirali & Toni-Kim Clarke & Riccardo E. Marioni & Gail Davies & Jonathan R. I. Coleman & Clara Alloza & Xueyi Shen & Miruna C. Barbu & Eleanor M. Wigmore & Jud, 2018. "Addendum: Genome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways," Nature Communications, Nature, vol. 9(1), pages 1-3, December.
    4. David M. Howard & Mark J. Adams & Masoud Shirali & Toni-Kim Clarke & Riccardo E. Marioni & Gail Davies & Jonathan R. I. Coleman & Clara Alloza & Xueyi Shen & Miruna C. Barbu & Eleanor M. Wigmore & Jud, 2018. "Genome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
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