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

PLoS ONE ◽  
2018 ◽  
Vol 13 (9) ◽  
pp. e0203896 ◽  
Author(s):  
Joey Ward ◽  
Nicholas Graham ◽  
Rona J. Strawbridge ◽  
Amy Ferguson ◽  
Gregory Jenkins ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Meta Analysis ◽  
Risk Scores ◽  
Antidepressant Response ◽  
Major Depressive ◽  
Polygenic Risk

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

2018 ◽  
Author(s):  
Joey Ward ◽  
Nicholas Graham ◽  
Rona Strawbridge ◽  
Amy Ferguson ◽  
Gregory Jenkins ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Meta Analysis ◽  
Antidepressant Medication ◽  
Research Network ◽  
Risk Scores ◽  
Antidepressant Response ◽  
Major Depressive ◽  
Polygenic Risk ◽  
Therapeutic Drugs

AbstractThere 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 = 783). 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.

scholarly journals Polygenic interactions with environmental adversity in the aetiology of major depressive disorder

2015 ◽  
Vol 46 (4) ◽  
pp. 759-770 ◽  
Author(s):  
N. Mullins ◽  
R. A. Power ◽  
H. L. Fisher ◽  
K. B. Hanscombe ◽  
J. Euesden ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Environmental Risk ◽  
Complex Traits ◽  
Risk Scores ◽  
Environment Interaction ◽  
Inverse Association ◽  
Major Depressive ◽  
Polygenic Risk ◽  
Gene Environment

BackgroundMajor depressive disorder (MDD) is a common and disabling condition with well-established heritability and environmental risk factors. Gene–environment interaction studies in MDD have typically investigated candidate genes, though the disorder is known to be highly polygenic. This study aims to test for interaction between polygenic risk and stressful life events (SLEs) or childhood trauma (CT) in the aetiology of MDD.MethodThe RADIANT UK sample consists of 1605 MDD cases and 1064 controls with SLE data, and a subset of 240 cases and 272 controls with CT data. Polygenic risk scores (PRS) were constructed using results from a mega-analysis on MDD by the Psychiatric Genomics Consortium. PRS and environmental factors were tested for association with case/control status and for interaction between them.ResultsPRS significantly predicted depression, explaining 1.1% of variance in phenotype (p= 1.9 × 10−6). SLEs and CT were also associated with MDD status (p= 2.19 × 10−4andp= 5.12 × 10−20, respectively). No interactions were found between PRS and SLEs. Significant PRSxCT interactions were found (p= 0.002), but showed an inverse association with MDD status, as cases who experienced more severe CT tended to have a lower PRS than other cases or controls. This relationship between PRS and CT was not observed in independent replication samples.ConclusionsCT is a strong risk factor for MDD but may have greater effect in individuals with lower genetic liability for the disorder. Including environmental risk along with genetics is important in studying the aetiology of MDD and PRS provide a useful approach to investigating gene–environment interactions in complex traits.

scholarly journals Dissection of major depressive disorder using polygenic risk scores for schizophrenia in two independent cohorts

2016 ◽  
Vol 6 (11) ◽  
pp. e938-e938 ◽  
Author(s):  
H C Whalley ◽  
M J Adams ◽  
L S Hall ◽  
T-K Clarke ◽  
A M Fernandez-Pujals ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Risk Scores ◽  
Major Depressive ◽  
Polygenic Risk

Discriminating bipolar depression from major depressive disorder with polygenic risk scores

2020 ◽  
pp. 1-8 ◽  
Author(s):  
David T. Liebers ◽  
Mehdi Pirooznia ◽  
Andrea Ganna ◽  
Fernando S. Goes ◽  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Clinical Features ◽  
Clinical Symptoms ◽  
Bipolar Depression ◽  
Risk Scores ◽  
Characteristic Analysis ◽  
Major Depressive ◽  
Polygenic Risk ◽  
Increased Risk

Abstract Background Although accurate differentiation between bipolar disorder (BD) and unipolar major depressive disorder (MDD) has important prognostic and therapeutic implications, the distinction is often challenging based on clinical grounds alone. In this study, we tested whether psychiatric polygenic risk scores (PRSs) improve clinically based classification models of BD v. MDD diagnosis. Methods Our sample included 843 BD and 930 MDD subjects similarly genotyped and phenotyped using the same standardized interview. We performed multivariate modeling and receiver operating characteristic analysis, testing the incremental effect of PRSs on a baseline model with clinical symptoms and features known to associate with BD compared with MDD status. Results We found a strong association between a BD diagnosis and PRSs drawn from BD (R2 = 3.5%, p = 4.94 × 10−12) and schizophrenia (R2 = 3.2%, p = 5.71 × 10−11) genome-wide association meta-analyses. Individuals with top decile BD PRS had a significantly increased risk for BD v. MDD compared with those in the lowest decile (odds ratio 3.39, confidence interval 2.19–5.25). PRSs discriminated BD v. MDD to a degree comparable with many individual symptoms and clinical features previously shown to associate with BD. When compared with the full composite model with all symptoms and clinical features PRSs provided modestly improved discriminatory ability (ΔC = 0.011, p = 6.48 × 10−4). Conclusions Our study demonstrates that psychiatric PRSs provide modest independent discrimination between BD and MDD cases, suggesting that PRSs could ultimately have utility in subjects at the extremes of the distribution and/or subjects for whom clinical symptoms are poorly measured or yet to manifest.

M74 HIGHER POLYGENIC RISK SCORES FOR SCHIZOPHRENIA MAY BE SUGGESTIVE OF NON-RESPONSE TO DRUGS FOR DEPRESSION IN PATIENTS WITH MAJOR DEPRESSIVE DISORDER

2019 ◽  
Vol 29 ◽  
pp. S206-S207
Author(s):  
Giuseppe Fanelli ◽  
Siegfried Kasper ◽  
Alexander Kautzky ◽  
Joseph Zohar ◽  
Daniel Souery ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Risk Scores ◽  
Major Depressive ◽  
Polygenic Risk
Sign in / Sign up

Export Citation Format

Share Document