Clinical characteristics indexing genetic differences in bipolar disorder – a systematic review | Molecular Psychiatry - Nature.com

Abstract

Bipolar disorder is a heterogenous condition with a varied clinical presentation. While progress has been made in identifying genetic variants associated with bipolar disorder, most common genetic variants have not yet been identified. More detailed phenotyping (beyond diagnosis) may increase the chance of finding genetic variants. Our aim therefore was to identify clinical characteristics that index genetic differences in bipolar disorder.

We performed a systematic review of all genome-wide molecular genetic, family, and twin studies investigating familial/genetic influences on the clinical characteristics of bipolar disorder. We performed an electronic database search of PubMed and PsycInfo until October 2022. We reviewed title/abstracts of 2693 unique records and full texts of 391 reports, identifying 445 relevant analyses from 142 different reports. These reports described 199 analyses from family studies, 183 analyses from molecular genetic studies and 63 analyses from other types of studies. We summarized the overall evidence per phenotype considering study quality, power, and number of studies.

We found moderate to strong evidence for a positive association of age at onset, subtype (bipolar I versus bipolar II), psychotic symptoms and manic symptoms with familial/genetic risk of bipolar disorder. Sex was not associated with overall genetic risk but could indicate qualitative genetic differences. Assessment of genetically relevant clinical characteristics of patients with bipolar disorder can be used to increase the phenotypic and genetic homogeneity of the sample in future genetic studies, which may yield more power, increase specificity, and improve understanding of the genetic architecture of bipolar disorder.

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Fig. 1: Flow diagram of the systematic review.

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Funding

The funding organizations had no impact on study design, data collection, analysis, or interpretation, or decision to submit the manuscript. Supported in part by the Stanley Center for Psychiatric Research. HL was supported by a VENI grant from the Talent Program of the Netherlands Organization of Scientific Research (NWO-ZonMW 09150161810021).

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Authors and Affiliations

  1. Department of Psychiatry and Interdisciplinary Center Psychopathology and Emotion regulation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

    Hanna M. van Loo & Luka Todorovic

  2. Department of Child and Adolescent Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Ymkje Anna de Vries & Luka Todorovic

  3. Department of Psychiatry, Brigham and Women's Hospital, Boston, MA, USA

    Jacob Taylor

  4. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA

    Jacob Taylor

  5. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA

    Jacob Taylor

  6. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Camille Dollinger

  7. Virginia Institute for Psychiatric and Behavioral Genetics and Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA

    Kenneth S. Kendler

Authors
  1. Hanna M. van Loo
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  6. Kenneth S. Kendler
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Contributions

HL, YV, JT, and KK contributed to the conception and design of the study. HL, YV, JT, LT, and CD contributed to the literature search and data extraction. HL, YV, and JT contributed to the analysis of the results. HL wrote the first draft of the manuscript, which was critically revised by all other authors. All authors approved the final draft of the manuscript.

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Correspondence to Hanna M. van Loo.

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