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

PloS One
Joey WardDaniel 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 < 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 stratifi...Continue Reading

References

Apr 3, 2010·The American Journal of Psychiatry·Rudolf UherPeter McGuffin
Apr 5, 2013·PLoS Genetics·Frank Dudbridge
Aug 15, 2013·International Psychogeriatrics·David C SteffensGuy G Potter
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Nov 15, 2017·Genome Medicine·Cathryn M Lewis, Evangelos Vassos

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Citations

Mar 29, 2019·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Caragh P StapletonUNKNOWN International Genetics and Translational Research in Transplantation Network
May 6, 2020·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Bettina MeiserTatiane Yanes
Mar 1, 2019·Philosophy, Ethics, and Humanities in Medicine : PEHM·A C PalkD J Stein
Aug 29, 2019·Psychiatry Investigation·Filippo CorponiAlessandro Serretti
Oct 24, 2019·Translational Psychiatry·Byron CreeseUNKNOWN AddNeuroMed consortium and the Alzheimer’s Disease Neuroimaging Initiative
Aug 27, 2019·F1000Research·Janice M Fullerton, John I Nurnberger
May 20, 2020·Genome Medicine·Cathryn M Lewis, Evangelos Vassos
Oct 15, 2020·JAMA Psychiatry·Graham K MurrayNaomi R Wray
Jan 30, 2021·Genome Medicine·Anna C F Lewis, Robert C Green
Nov 13, 2020·Progress in Neuro-psychopharmacology & Biological Psychiatry·Giuseppe FanelliChiara Fabbri
Jul 25, 2021·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Joanna M BiernackaVictor M Karpyak
Dec 26, 2021·Clinical Pharmacology and Therapeutics·Danielle JohnsonBritt I Drögemöller

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Methods Mentioned

BETA
genotyping

Software Mentioned

metaphor
PLINK
REML
GENDEP
uni
rma

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