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Discriminating bipolar depression from major depressive disorder with polygenic risk scores

Published online by Cambridge University Press:  17 February 2020

David T. Liebers ,
Mehdi Pirooznia ,
Andrea Ganna ,
Fernando S. Goes Open the ORCID record for Fernando S. Goes [Opens in a new window]  and
Bipolar Genome Study (BiGS)
David T. Liebers
Affiliation:
Harvard Medical School, Boston, MA 02115, USA
Mehdi Pirooznia
Affiliation:
Department of Psychiatry and Behavioral Sciences, Johns Hopkins Institute of Medicine, Baltimore, MD 21205, USA
Andrea Ganna
Affiliation:
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Fernando S. Goes*
Affiliation:
Department of Psychiatry and Behavioral Sciences, Johns Hopkins Institute of Medicine, Baltimore, MD 21205, USA
*
Author for correspondence: Fernando S. Goes, E-mail: fgoes1@jhmi.edu
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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.

Keywords

Bipolar disordergeneticsGWASmajor depressive disordermood disorderspolygenic risk scores
Type
Original Articles
Information
Psychological Medicine , Volume 51 , Issue 9 , July 2021 , pp. 1451 - 1458
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Copyright
Copyright © The Author(s) 2020. Published by Cambridge University Press

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