Evidence map›Paper›PMID 39806801›Full record

ArticleThe British journal of psychiatry : the journal of mental science2025

Identifying genetic differences between bipolar disorder and major depression through multiple genome-wide association analyses.

Georgia Panagiotaropoulou, Kajsa-Lotta Georgii Hellberg, Jonathan R I Coleman, Darsol Seok, Janos Kalman, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, iPSYCH Study Consortium, Philip B Mitchell, Peter R Schofield and 47 more

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Article in The British journal of psychiatry : the journal of mental science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Polygenic scores in psychiatric research and clinical practice.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026
    Article
  2. Article
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

57 authors.

Georgia PanagiotaropoulouDepartment of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Germany.ORCID https://orcid.org/0000-0001-9516-6158
Kajsa-Lotta Georgii HellbergInstitute of Biological Psychiatry, Mental Health Center Sct Hans, Copenhagen University Hospital, Denmark; and Faculty of Health and Medical Sciences, Copenhagen University, Denmark.
Jonathan R I ColemanSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, UK; and NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK.ORCID https://orcid.org/0000-0002-6759-0944
Darsol SeokDepartment of Psychiatry, University of California, USA.
Janos KalmanInstitute for Psychiatric Phenomics and Genomics, Ludwig Maximilian University, Germany.ORCID https://orcid.org/0000-0003-0930-4214
Bipolar Disorder Working Group of the Psychiatric Genomics Consortium
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
iPSYCH Study Consortium
Philip B MitchellDiscipline of Psychiatry and Mental Health, School of Medicine and Health, University of New South Wales, Australia.
Peter R SchofieldNeuroscience Research Australia, Sydney, Australia; and School of Biomedical Sciences, University of New South Wales, Australia.
Andreas J ForstnerInstitute of Human Genetics, University of Bonn, School of Medicine and University Hospital Bonn, Germany; and Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Germany.
Michael BauerDepartment of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus Medical Faculty, Technische Universität Dresden, Germany.
Laura J ScottDepartment of Biostatistics and Center for Statistical Genetics, School of Public Health, University of Michigan, USA.
Carlos N PatoDepartment of Psychiatry, Rutgers Health, Rutgers University, USA.
Michele T PatoDepartment of Psychiatry, Rutgers Health, Rutgers University, USA.
Qingqin S LiNeuroscience Research and Development, Janssen, Raritan, New Jersey, USA.
George KirovDivision of Psychological Medicine and Clinical Neuroscience, Cardiff University, UK.ORCID https://orcid.org/0000-0002-3427-3950
Mikael LandénDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden; and Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden.ORCID https://orcid.org/0000-0002-4496-6451
Lina JonssonDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.ORCID https://orcid.org/0000-0002-3175-103X
Bertram Müller-MyhsokLaboratory for Statistical Genetics, Max Planck Institute of Psychiatry, Germany.
Jordan W SmollerPsychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA; Center for Precision Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA; and Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
Elisabeth B BinderDepartment of Genes and Environment, Max Planck Institute of Psychiatry, Germany.
Tanja M BrücklDepartment of Genes and Environment, Max Planck Institute of Psychiatry, Germany.
Darina CzamaraDepartment of Genes and Environment, Max Planck Institute of Psychiatry, Germany.
Sandra Van der AuweraDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Germany.
Hans J GrabeDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Germany.
Georg HomuthInterfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine Greifswald, Germany.
Carsten O SchmidtInstitute for Community Medicine, Study of Health in Pomerania - Quality in the Health Sciences (SHIP-QIHS), University Medicine Greifswald, Germany.
James B PotashDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, USA.
J Raymond DePauloDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, USA.
Fernando S GoesDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, USA.
Dean F MacKinnonDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, USA.
Francis M MondimoreDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, USA.
Myrna M WeissmanDepartment of Epidemiology, Columbia University Mailman School of Public Health, USA; Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons, USA; and Division of Translational Epidemiology & Mental Health Equity, New York State Psychiatric Institute, New York, New York, USA.
Jianxin ShiDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
Mark A FryeDepartment of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota, USA.
Joanna M BiernackaDepartment of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota, USA; and Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA.
Andreas ReifDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University Frankfurt, University Hospital Frankfurt, Germany.
Stephanie H WittDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany.
René R KahnDepartment of Psychiatry and Behavioral Health System, Icahn School of Medicine at Mount Sinai, USA.
Marco M BoksDepartment of Psychiatry, University Medical Center Utrecht, The Netherlands.
Michael J OwenCentre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, UK.
Katherine Gordon-SmithPsychological Medicine, University of Worcester, UK.ORCID https://orcid.org/0000-0003-4083-1143
Brittany L MitchellMental Health and Neuroscience Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Nicholas G MartinMental Health and Neuroscience Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Sarah E MedlandMental Health and Neuroscience Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Lisa JonesThree Counties Medical School, University of Worcester, UK.ORCID https://orcid.org/0000-0002-5122-8334
James A KnowlesDepartment of Genetics, Rutgers University, USA.
Douglas F LevinsonDepartment of Psychiatry & Behavioral Sciences, Stanford University, USA.ORCID https://orcid.org/0000-0001-8223-1301
Michael C O'DonovanCentre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, UK.ORCID https://orcid.org/0000-0001-7073-2379
Cathryn M LewisSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, UK; and NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK.ORCID https://orcid.org/0000-0002-8249-8476
Gerome BreenSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, UK; and NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK.
Thomas WergeInstitute of Biological Psychiatry, Mental Health Center Sct Hans, Copenhagen University Hospital, Denmark; and Section for Geogenetics, GLOBE Institute, Faculty of Health and Medical Sciences, Copenhagen University, Denmark.
Andrew J SchorkInstitute of Biological Psychiatry, Mental Health Center Sct Hans, Copenhagen University Hospital, Denmark.
Roel A OphoffCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, USA; and Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, USA.ORCID https://orcid.org/0000-0002-8287-6457
Stephan RipkeDepartment of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Germany; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA; and German Center for Mental Health (DZPG), Berlin, Germany.
Loes Olde LoohuisCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, USA; Department of Human Genetics, University of California Los Angeles, USA; and Department of Computational Medicine, University of California Los Angeles, USA.ORCID https://orcid.org/0000-0002-3327-7837

Funding

A Latin American biobank for large-scale genetics research on severe mental illnessR01MH123157 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FREIMER, NELSON B., LOPEZ JARAMILLO, CARLOS · 2020 to 2025
$10.6M
5/7 Psychiatric Genomics Consortium: Advancing Discovery and ImpactR01MH124873 · NIMH · CARDIFF UNIVERSITY · PI LEWIS, CATHRYN, O'DONOVAN, MICHAEL · 2021 to 2025
$2.6M
Accelerating the Diagnosis of Bipolar Disorder Using Genetic and Phenotypic SignaturesR00MH116115 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI OLDE LOOHUIS, LOES MARLEIN · 2020 to 2022
$747k
Accelerating the diagnosis of bipolar disorder using genetic and phenotypic signaturesK99MH116115 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI OLDE LOOHUIS, LOES MARLEIN · 2018 to 2019
$257k
NIMH NIH HHS 1/3 Psychiatric GWAS Consortium: Advancing DiscoveNIMH NIH HHS 1R01MH124873-01 (to SR)NIMH NIH HHS K99 MH116115NIMH NIH HHS R00 MH116115NIMH NIH HHS R00MH116115 (to LMOL)NIMH NIH HHS R01 MH123157NIMH NIH HHS R01 MH124873
6 · The paper itself

Abstract

backgroundAccurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).

aimsWe use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.

methodBased on individual genotypes from case-control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case-case-control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.

resultsAlthough our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015,

conclusionsWe find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.

Indexed as

Bipolar DisorderGenome-Wide Association StudyMajor Depressive DisorderAdultCase-Control StudiesDiagnosis, DifferentialFemaleGenetic Predisposition to DiseaseHumansMaleMiddle AgedMultifactorial InheritancePolymorphism, Single NucleotideBipolar disorderearly differential diagnosisgenome-wide association analysismajor depressive disorderpolygenic risk scoring

Identifiers

PMID39806801
PMCPMC12337998

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.