Evidence map›Paper›PMID 35048876›Full record

ArticleThe British journal of psychiatry : the journal of mental science2021

Characterisation of age and polarity at onset in bipolar disorder.

Janos L Kalman, Loes M Olde Loohuis, Annabel Vreeker, Andrew McQuillin, Eli A Stahl, Douglas Ruderfer, Maria Grigoroiu-Serbanescu, Georgia Panagiotaropoulou, Stephan Ripke, Tim B Bigdeli and 166 more

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Article in The British journal of psychiatry : the journal of mental science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
4.9field-weighted citation impact, top 4% of its field
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

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Characterisation of serious mental illness trajectories through transdiagnostic clinical features.The British journal of psychiatry : the journal of mental science · 2026
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  5. Review
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  11. The Swedish bipolar collection (SWEBIC).International journal of bipolar disorders · 2025
    Article
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  17. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

176 authors at 20 institutions in 17 countries.

Janos L KalmanInstitute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Germany; Department of Psychiatry and Psychotherapy, University Hospital Munich, Germany; and International Max Planck Research School for Translational Psychiatry, Germany.ORCID 0000-0003-0930-4214
Loes M Olde LoohuisCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, USA.
Annabel VreekerDepartment of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Centre-Sophia Children's Hospital, the Netherlands.
Andrew McQuillinDivision of Psychiatry, University College London, UK.
Eli A StahlDivision of Psychiatric Genomics, Mount Sinai School of Medicine, USA.
Douglas RuderferDivision of Genetic Medicine, Department of Medicine, Vanderbilt Genetics Institute, Vanderbilt University Medical Center, USA; Department of Biomedical Informatics, Vanderbilt University Medical Center, USA; and Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, USA.
Maria Grigoroiu-SerbanescuAlexandru Obregia Clinical Psychiatric Hospital, Bucharest, Romania.
Georgia PanagiotaropoulouDepartment of Psychiatry and Psychotherapy, Charite - Universitätsmedizin, Germany.
Stephan RipkeAnalytic and Translational Genetics Unit, Massachusetts General Hospital, USA; and Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, USA.
Tim B BigdeliDepartment of Psychiatry and Behavioral Sciences, SUNY Downstate Health Sciences University, USA; and VA NY Harbor Healthcare System, USA.
Frederike SteinDepartment of Psychiatry and Psychotherapy, Philipps-University Marburg, Germany.
Tina MellerDepartment of Psychiatry and Psychotherapy, Philipps-University Marburg, Germany; and Center for Mind, Brain and Behavior (CMBB), Germany.
Susanne MeinertInstitute for Translational Psychiatry, Westfälische Wilhelms-Universität Münster, Germany; and Institute for Translational Neuroscience, University of Münster, Germany.
Helena PelinInternational Max Planck Research School for Translational Psychiatry, Germany; and Max Planck Institute of Psychiatry, Germany.
Fabian StreitDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Germany.
Sergi PapiolInstitute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Germany; Department of Psychiatry and Psychotherapy, University Hospital Munich, Germany; and Centro de Investigación Biomedica en Red de Salud Mental (CIBERSAM), Spain.
Mark J AdamsDivision of Psychiatry, University of Edinburgh, UK.ORCID 0000-0002-3599-6018
Rolf AdolfssonDepartment of Clinical Sciences, Medical Faculty, Umeå University, Sweden.
Kristina AdorjanInstitute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Germany; and Department of Psychiatry and Psychotherapy, University Hospital Munich, Germany.ORCID 0000-0001-7501-9556
Ingrid AgartzDepartment of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Sweden; Department of Psychiatric Research, Diakonhjemmet Hospital, Norway; and NORMENT Centre, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Norway.
Sofie R AminoffDivision of Mental Health and Addiction, Oslo University Hospital, Norway; and NORMENT Centre, Inst of Clinical Medicine, University of Oslo, Norway.
Heike Anderson-SchmidtDepartment of Psychiatry and Psychotherapy, University Medical Center Göttingen, Germany.
Ole A AndreassenNORMENT Centre, Inst of Clinical Medicine, University of Oslo, Norway; and Division of Mental Health and Addiction, Oslo University Hosptial, Norway.
Raffaella ArdauUnit of Clinical Pharmacology, University Hospital Agency of Cagliari, Italy.
Jean-Michel AubryFaculty of medicine, University of Geneva, Switzerland; and Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Germany.
Ceylan BalabanDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Germany.
Nicholas BassDivision of Psychiatry, University College London, UK.
Bernhard T BauneDepartment of Psychiatry, University of Münster, Germany; Department of Psychiatry, Melbourne Medical School, The University of Melbourne, Australia; The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Australia; and Discipline of Psychiatry, Adelaide Medical School, The University of Adelaide, Australia.
Frank BellivierUniversite de Paris, France; INSERM UMRS 1144, France; and DMU Neurosciences, GHU Lariboisière Fernand Widal, Departement de Psychiatrie, APHP, France.
Antoni BenabarreHospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Spain.
Susanne BengesserDepartment of Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Austria.
Wade H BerrettiniPsychiatry, University of Pennsylvania, USA.
Marco P BoksPsychiatry, UMC Utrecht Brain Center, the Netherlands.
Evelyn J BrometDepartment of Psychiatry, Stony Brook University, USA.
Katharina BroschDepartment of Psychiatry and Psychotherapy, Philipps-University Marburg, Germany.
Monika BuddeInstitute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Germany.
William ByerleyPsychiatry, University of California San Francisco, USA.
Pablo CervantesDepartment of Psychiatry, McGill University, Canada.
Catina ChillottiUnit of Clinical Pharmacology, University Hospital Agency of Cagliari, Italy.
Sven CichonDepartment of Biomedicine, University of Basel, Switzerland; Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Germany; Institute of Medical Genetics and Pathology, University Hospital Basel, Switzerland; and Institute of Neuroscience and Medicine (INM-1), Research Centre Julich, Germany.
Scott R ClarkDiscipline of Psychiatry, University of Adelaide, Australia; and Bazil Hetzel Institute, Australia.
Ashley L ComesInstitute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Germany; Department of Psychiatry and Psychotherapy, University Hospital Munich, Germany; and International Max Planck Research School for Translational Psychiatry, Germany.
Aiden CorvinDepartment of Psychiatry & Trinity Translational Medicine Institute, Trinity College Dublin, Ireland.
William CoryellUniversity of Iowa Hospitals and Clinics, USA.
Nick CraddockMedical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, UK.
David W CraigTranslational Genomics, USC, USA.
Paul E CroarkinDepartment of Psychiatry and Psychology, Mayo Clinic, USA.
Cristiana CruceanuDepartment of Translational Research, Max Planck Institute of Psychiatry, Germany.
Piotr M CzerskiDepartment of Psychiatric Genetics, Poznan University of Medical Sciences, Poland.
Nina DalknerDepartment of Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Austria.
Udo DannlowskiInstitute for Translational Psychiatry, Westfälische Wilhelms-Universität Münster, Germany.
Franziska DegenhardtInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Germany; and Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Essen, University of Duisburg-Essen, Germany.
Maria Del ZompoDepartment of Biomedical Science, Section of Neuroscience & Clinical Pharmacology, University of Cagliari, Italy; and Unit of Clinical Pharmacology, University Hospital Agency of Cagliari, Italy.
J Raymond DePauloDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, USA.
Srdjan DjurovicDepartment of Medical Genetics, Oslo University Hospital Ullevål, Norway; and NORMENT, Department of Clinical Science, University of Bergen, Norway.
Howard J EdenbergDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, USA.ORCID 0000-0003-0344-9690
Mariam Al EissaDivision of Psychiatry, University College London, UK.
Torbjørn ElvsåshagenNORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Norway.
Bruno EtainUniversite de Paris, France; INSERM UMRS 1144, France; and DMU Neurosciences, GHU Lariboisière Fernand Widal, Departement de Psychiatrie, APHP, France.ORCID 0000-0002-5377-1488
Ayman H FanousDepartment of Psychiatry and Behavioral Sciences, SUNY Downstate Health Sciences University, USA; and VA NY Harbor Healthcare System, USA.
Frederike FellendorfDepartment of Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Austria.
Alessia FiorentinoDivision of Psychiatry, University College London, UK.
Andreas J ForstnerInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Germany; and Centre for Human Genetics, University of Marburg, Germany.
Mark A FryeDepartment of Psychiatry and Psychology, Mayo Clinic, USA.
Janice M FullertonNeuroscience Research Australia, Australia; and School of Medical Sciences, University of New South Wales, Australia.
Katrin GadeDepartment of Psychiatry and Psychotherapy, University Medical Center Göttingen, Germany.ORCID 0000-0001-8629-0579
Julie GarnhamNova Scotia Health Authority, Canada.
Elliot GershonDepartment of Psychiatry and Behavioral Neuroscience, University of Chicago, USA; and Department of Human Genetics, University of Chicago, USA.
Michael GillDepartment of Psychiatry & Trinity Translational Medicine Institute, Trinity College Dublin, Ireland.
Fernando S GoesDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, USA.
Katherine Gordon-SmithPsychological Medicine, University of Worcester, UK.ORCID 0000-0003-4083-1143
Paul GrofMood Disorders Centre of Ottawa, Canada; and Department of Psychiatry, University of Toronto, Canada.
Jose Guzman-ParraMental Health Department, University Regional Hospital, Biomedicine Institute (IBIMA), Spain.
Tim HahnInstitute for Translational Psychiatry, Westfälische Wilhelms-Universität Münster, Germany.
Roland HaslerCell Biology, SUNY Downstate Medical Center College of Medicine, USA; and Institute for Genomic Health, SUNY Downstate Medical Center College of Medicine, USA.
Maria HeilbronnerInstitute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Germany.
Urs HeilbronnerInstitute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Germany.ORCID 0000-0001-7135-762X
Stephane JamainUniversite Paris Est Creteil, France; and INSERM U 955, Neuropsychiatrie Translationnelle, France.
Esther JimenezHospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Spain.
Ian JonesMedical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, UK.
Lisa JonesPsychological Medicine, University of Worcester, UK.ORCID 0000-0002-5122-8334
Lina JonssonDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sweden.
Rene S KahnDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, USA.
John R KelsoeDepartment of Psychiatry, University of California San Diego, USA.
James L KennedyDepartment of Psychiatry, University of Toronto, Canada; The Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Canada; and Institute of Medical Science, University of Toronto, Canada.
Tilo KircherDepartment of Psychiatry and Psychotherapy, Philipps-University Marburg, Germany.
George KirovMedical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, UK.ORCID 0000-0002-3427-3950
Sarah Kittel-SchneiderDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Germany; and Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital Wurzburg, Germany.
Farah Klöhn-SaghatolislamInstitute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Germany.
James A KnowlesCell Biology, SUNY Downstate Medical Center College of Medicine, USA; and Institute for Genomic Health, SUNY Downstate Medical Center College of Medicine, USA.
Thorsten M KranzDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Germany.
Trine Vik LagerbergNORMENT Centre, Division of Mental Health and Addiction, Oslo University Hosptial, Norway.
Mikael LandenDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sweden; and Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden.
William B LawsonDepartment of Psychiatry and Behavioral Sciences, Howard University Hospital, USA.
Marion LeboyerUniversite Paris Est Creteil, France; and INSERM U 955, Neuropsychiatrie Translationnelle, France.
Qingqin S LiNeuroscience, Janssen Research & Development, USA.
Mario MajDepartment of Psychiatry, University of Campania 'Luigi Vanvitelli', Italy.
Dolores MalaspinaDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, USA; and Department of Genetics & Genomics, Icahn School of Medicine at Mount Sinai, USA.
Mirko ManchiaUnit of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, Italy and Department of Pharmacology, Dalhousie University, Canada.
Fermin MayoralMental Health Department, University Regional Hospital, Biomedicine Institute (IBIMA), Spain.
Susan L McElroyResearch Institute, Lindner Center of HOPE, USA.
Melvin G McInnisDepartment of Psychiatry, University of Michigan, USA.
Andrew M McIntoshDivision of Psychiatry, University of Edinburgh, UK.ORCID 0000-0002-0198-4588
Helena MedeirosInstitute for Genomic Health, SUNY Downstate Medical Center College of Medicine, USA.
Ingrid MelleNORMENT Centre, Division of Mental Health and Addiction, Institute of Clinical Medicine and Diakonhjemmet Hospital, University of Oslo, Norway; and Division of Mental Health and Addiction, Oslo University Hospital, Norway.
Vihra MilanovaPsychiatric Clinic, Alexander University Hospital, Bulgaria.
Philip B MitchellSchool of Psychiatry, University of New South Wales, Australia.ORCID 0000-0002-7954-5235
Palmiero MonteleoneDepartment of Medicine, Surgery and Dentistry 'Scuola Medica Salernitana', University of Salerno, Italy.
Alessio Maria MonteleoneDepartment of Psychiatry, University of Campania 'Luigi Vanvitelli', Italy.
Markus M NöthenInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Germany.
Tomas NovakNational Institute of Mental Health, Czech Republic.
John I NurnbergerPsychiatry, Indiana University School of Medicine, USA.ORCID 0000-0002-7674-1767
Niamh O'BrienDivision of Psychiatry, University College London, UK.
Kevin S O'ConnellDivision of Mental Health and Addiction, Oslo University Hospital, Norway; and NORMENT Centre, Inst of Clinical Medicine, University of Oslo, Norway.
Claire O'DonovanDepartment of Psychiatry, Dalhousie University, Canada.
Michael C O'DonovanMedical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, UK.
Nils OpelInstitute for Translational Psychiatry, Westfälische Wilhelms-Universität Münster, Germany.
Abigail OrtizDepartment of Psychiatry, University of Toronto, Toronto, Canada; and Centre for Addiction and Mental Health, Toronto, Canada.ORCID 0000-0001-6886-767X
Michael J OwenMedical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, UK.
Erik PålssonDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sweden.
Carlos PatoInstitute for Genomic Health, SUNY Downstate Medical Center College of Medicine, USA.
Michele T PatoInstitute for Genomic Health, SUNY Downstate Medical Center College of Medicine, USA.
Joanna PawlakDepartment of Psychiatric Genetics, Poznan University of Medical Sciences, Poland.
Julia-Katharina PfarrDepartment of Psychiatry and Psychotherapy, Philipps-University Marburg, Germany.
Claudia PisanuDepartment of Biomedical Science, Section of Neuroscience & Clinical Pharmacology, University of Cagliari, Italy.
James B PotashDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, USA.
Mark H RapaportDepartment of Psychiatry and Behavioral Sciences, Emory University, USA.
Daniela Reich-ErkelenzInstitute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Germany.
Andreas ReifDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Germany.
Eva ReininghausDepartment of Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Austria.
Jonathan ReppleInstitute for Translational Psychiatry, Westfälische Wilhelms-Universität Münster, Germany.
Hélène Richard-LepourielDepartment of Psychiatry, Geneva University Hospitals, Switzerland.
Marcella RietschelDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Germany.
Kai RingwaldDepartment of Psychiatry and Psychotherapy, Philipps-University Marburg, Germany.
Gloria RobertsSchool of Psychiatry, University of New South Wales, Australia.ORCID 0000-0002-1966-5120
Guy RouleauMontreal Neurological Institute, Canada and Department of Neurology, McGill University, Canada.
Sabrina SchauppInstitute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Germany.
William A ScheftnerDepartment of Psychiatry, Rush Medical College, USA.
Simon SchmittDepartment of Psychiatry and Psychotherapy, Philipps-University Marburg, Germany.
Peter R SchofieldNeuroscience Research Australia, Australia; and School of Medical Sciences, University of New South Wales, Australia.
K Oliver SchubertDiscipline of Psychiatry, University of Adelaide, Australia; and Northern Adelaide Mental Health Service, SA Health, Australia.
Eva C SchulteInstitute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Germany; and Department of Psychiatry and Psychotherapy, University Hospital Munich, Germany.ORCID 0000-0003-3105-5672
Barbara SchweizerDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, USA.
Fanny SennerInstitute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Germany; and Department of Psychiatry and Psychotherapy, University Hospital Munich, Germany.
Giovanni SeverinoDepartment of Biomedical Science, Section of Neuroscience & Clinical Pharmacology, University of Cagliari, Italy.
Sally SharpDivision of Psychiatry, University College London, UK.
Claire SlaneyNova Scotia Health Authority, Canada.
Olav B SmelandDivision of Mental Health and Addiction, Oslo University Hospital, Norway; and NORMENT Centre, Inst of Clinical Medicine, University of Oslo, Norway.
Janet L SobellPsychiatry and the Behavioral Sciences, University of Southern California, USA.
Alessio SquassinaDepartment of Psychiatry, Dalhousie University, Canada; and Department of Biomedical Science, Section of Neuroscience & Clinical Pharmacology, University of Cagliari, Italy.
Pavla StopkovaNational Institute of Mental Health, Czech Republic.
John StraussDepartment of Psychiatry, University of Toronto, Canada; The Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Canada; and Institute of Medical Science, University of Toronto, Canada.
Alfonso TortorellaDepartment of Psychiatry, University of Perugia, Italy.
Gustavo TureckiDepartment of Psychiatry, McGill University, Canada; and Douglas Institute, McGill University, Canada.
Joanna Twarowska-HauserDepartment of Psychiatric Genetics, Poznan University of Medical Sciences, Poland.
Marin VeldicDepartment of Psychiatry and Psychology, Mayo Clinic, USA.
Eduard VietaHospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Spain.
John B VincentDepartment of Psychiatry, University of Toronto, Canada; The Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Canada; and Institute of Medical Science, University of Toronto, Canada.
Wei XuDalla Lana School of Public Health, Biostatistics Division, University of Toronto, Canada.
Clement C ZaiDepartment of Psychiatry, University of Toronto, Canada; The Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Canada; Institute of Medical Science, University of Toronto, Canada; Laboratory Medicine and Pathobiology, University of Toronto, Canada; and Harvard T.H. Chan School of Public Health, USA.
Peter P ZandiDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, USA.
Psychiatric Genomics Consortium (PGC) Bipolar Disorder Working Group
International Consortium on Lithium Genetics (ConLiGen)
Colombia-US Cross Disorder Collaboration in Psychiatric Genetics
Arianna Di FlorioMedical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, UK.
Jordan W SmollerPsychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry and Center for Genomic Medicine, Massachusetts General Hospital, USA; and Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, USA.
Joanna M BiernackaDepartment of Psychiatry and Psychology, Mayo Clinic, USA; and Department of Health Sciences Research, Mayo Clinic, USA.
Francis J McMahonHuman Genetics Branch, Intramural Research Program, National Institute of Mental Health, USA.
Martin AldaNational Institute of Mental Health, Czech Republic; and Department of Psychiatry, Dalhousie University, Canada.ORCID 0000-0001-9544-3944
Bertram Müller-MyhsokMax Planck Institute of Psychiatry, Germany.
Nikolaos KoutsoulerisDepartment of Psychiatry and Psychotherapy, University Hospital Munich, Germany; Max Planck Institute of Psychiatry, Germany; and Institute of Psychiatry, Psychology and Neuroscience, Kings College London, UK.
Peter FalkaiDepartment of Psychiatry and Psychotherapy, University Hospital Munich, Germany.
Nelson B FreimerCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, USA; and Human Genetics, University of California Los Angeles, USA.
Till F M AndlauerDepartment of Neurology, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Germany.ORCID 0000-0002-2917-5889
Thomas G SchulzeInstitute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Germany; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Germany; Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Germany; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, USA; and Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, USA.
Roel A OphoffCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, USA; Human Genetics, University of California Los Angeles, USA; and Psychiatry, Erasmus University Medical Center, the Netherlands.
Max Planck Institute of Psychiatry · DEOslo University Hospital · NOPhilipps University of Marburg · DESUNY Downstate Health Sciences University · USCardiff University · GBJohns Hopkins University · USUniversity College London · GBCentre for Addiction and Mental Health · CAGoethe University Frankfurt · DEUniversity of Münster · DECentro de Investigación Biomédica en Red de Salud Mental · ESDalhousie University · CAInserm · FRMedical University of Graz · ATUniversity of Bonn · DEUNSW Sydney · AUWinnMed · USLMU Klinikum · DEMünchen Klinik · DEPoznan University of Medical Sciences · PL

Funding

African Ancestry Genomic Psychiatry CohortR01MH104964 · NIMH · SUNY DOWNSTATE MEDICAL CENTER · PI BIGDELI, TIM BERNARD, FANOUS, AYMAN H · 2015 to 2024
$16.7M
Latino Ancestry Genomic Psychiatry CohortR01MH123451 · NIMH · SUNY DOWNSTATE MEDICAL CENTER · PI BIGDELI, TIM BERNARD, FANOUS, AYMAN H · 2020 to 2025
$7.1M
Genetics of Severe Mental IllnessR01MH113078 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BEARDEN, CARRIE E, FREIMER, NELSON B. · 2017 to 2021
$5.8M
Neurodevelopment and Psychosis in the 22q11.2 Copy Number VariantsR37MH085953 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CARRIE E BEARDEN · 2023 to 2026
$2.9M
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
Medical Research Council G1000708NIMH NIH HHS K99 MH116115NIMH NIH HHS R00 MH116115NIMH NIH HHS R01 MH104964NIMH NIH HHS R01 MH113078NIMH NIH HHS R01 MH123451NIMH NIH HHS R01 MH124873NIMH NIH HHS R37 MH085953Wellcome Trust
6 · The paper itself

Abstract

backgroundStudying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.

aimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.

methodGenome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.

resultsEarlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = -0.34 years, s.e. = 0.08), major depression (β = -0.34 years, s.e. = 0.08), schizophrenia (β = -0.39 years, s.e. = 0.08), and educational attainment (β = -0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.

conclusionsAAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.

Indexed as

Autism Spectrum DisorderBipolar DisorderMajor Depressive DisorderAge of OnsetGenome-Wide Association StudyHumansMultifactorial Inheritanceage at onsetBipolar disorderGWASpolarity at onsetpolygenic score

Identifiers

PMID35048876
PMCPMC8636611
OpenAlexW3194462435

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