Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study

doi:10.1111/bdi.12659

Multicenter Study

. 2019 Feb;21(1):68-75.

doi: 10.1111/bdi.12659. Epub 2018 Jun 28.

Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study

Janos L Kalman^{1

2

3}, Sergi Papiol^{1

2

4}, Andreas J Forstner^{5

6

7}, Urs Heilbronner^{1

8}, Franziska Degenhardt⁵, Jana Strohmaier⁹, Mazda Adli¹⁰, Kristina Adorjan^{1

2}, Nirmala Akula¹¹, Martin Alda¹², Heike Anderson-Schmidt^{1

8}, Till Fm Andlauer¹³, Ion-George Anghelescu¹⁴, Raffaella Ardau¹⁵, Bárbara Arias¹⁶, Volker Arolt¹⁷, Jean-Michel Aubry¹⁸, Lena Backlund¹⁹, Kim Bartholdi¹, Michael Bauer²⁰, Bernhard T Baune²¹, Thomas Becker²², Frank Bellivier²³, Antonio Benabarre²⁴, Susanne Bengesser²⁵, Abesh Kumar Bhattacharjee²⁶, Joanna M Biernacka²⁷, Armin Birner²⁵, Clara Brichant-Petitjean²³, Monika Budde¹, Pablo Cervantes²⁸, Caterina Chillotti¹⁵, Sven Cichon^{5

7}, Scott R Clark²¹, Francesc Colom²⁹, Ashley L Comes^{1

3}, Cristiana Cruceanu^{13

28}, Piotr M Czerski³⁰, Udo Dannlowski¹⁷, Alexandre Dayer¹⁸, Maria Del Zompo³¹, Jay Raymond DePaulo³², Detlef E Dietrich³³, Bruno Étain²³, Thomas Ethofer³⁴, Peter Falkai², Andreas Fallgatter³⁴, Christian Figge³⁵, Laura Flatau¹, Here Folkerts³⁶, Louise Frisen¹⁹, Mark A Frye²⁷, Janice M Fullerton^{37

38}, Katrin Gade^{1

8}, Sébastien Gard³⁹, Julie S Garnham¹², Fernando S Goes³², Maria Grigoroiu-Serbanescu⁴⁰, Anna Gryaznova¹, Maria Hake¹, Joanna Hauser³⁰, Stefan Herms^{5

7}, Per Hoffmann^{5

7}, Liping Hou¹¹, Markus Jäger²², Stephane Jamain⁴¹, Esther Jiménez²⁴, Georg Juckel⁴², Jean-Pierre Kahn⁴³, Layla Kassem⁴⁴, John Kelsoe²⁶, Sarah Kittel-Schneider⁴⁵, Sebastian Kliwicki⁴⁶, Farah Klohn-Sagatholislam^{1

2}, Manfred Koller⁴⁷, Barbara König⁴⁸, Carsten Konrad⁴⁹, Nina Lackner²⁵, Gonzalo Laje¹¹, Mikael Landén^{50

51}, Fabian U Lang²², Catharina Lavebratt³⁹, Marion Leboyer^{41

52}, Susan G Leckband⁵³, Mario Maj⁵⁴, Mirko Manchia^{55

56}, Lina Martinsson⁵⁷, Michael J McCarthy²⁶, Susan L McElroy⁵⁸, Francis J McMahon¹¹, Philip B Mitchell^{59

60}, Marina Mitjans⁶¹, Francis M Mondimore³², Palmiero Monteleone^{54

62}, Vanessa Nieratschker³⁴, Caroline M Nievergelt²⁶, Tomas Novák^{63

64}, Urban Ösby⁶⁵, Andrea Pfennig²⁰, James B Potash⁶⁶, Daniela Reich-Erkelenz¹, Andreas Reif⁴⁵, Jens Reimer⁶⁷, Eva Reininghaus²⁵, Markus Reitt⁸, Stephan Ripke^{10

68}, Guy A Rouleau²⁸, Janusz K Rybakowski⁴⁶, Martin Schalling¹⁹, Harald Scherk⁶⁹, Max Schmauß⁷⁰, Peter R Schofield^{37

38}, K Oliver Schubert²¹, Eva C Schulte^{1

2}, Sybille Schulz⁶⁷, Fanny Senner^{1

2}, Giovanni Severino³¹, Tatyana Shekhtman²⁶, Paul D Shilling²⁶, Christian Simhandl^{71

72}, Claire M Slaney¹², Carsten Spitzer⁷³, Alessio Squassina³¹, Thomas Stamm^{10

74}, Sophia Stegmaier³⁴, Sebastian Stierl⁷⁵, Pavla Stopkova⁶³, Andreas Thiel⁴⁹, Sarah K Tighe⁶⁶, Alfonso Tortorella⁷⁶, Gustavo Turecki⁷⁷, Eduard Vieta²⁴, Julia Veeh⁴⁵, Martin von Hagen⁷⁸, Moritz E Wigand²², Jens Wiltfang⁸, Stephanie Witt⁹, Adam Wright^{59

60}, Peter P Zandi³², Jörg Zimmermann⁶⁷, Markus Nöthen⁵, Marcella Rietschel⁹, Thomas G Schulze¹

Affiliations

¹ Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany.
² Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Munich, Germany.
³ International Max Planck Research School for Translational Psychiatry (IMPRS-TP), Munich, Germany.
⁴ Instituto de Salud Carlos III, Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain.
⁵ Institute of Human Genetics, University of Bonn and Department of Genomics, Life & Brain Center, Bonn, Germany.
⁶ Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
⁷ Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland.
⁸ Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August University Göttingen, Göttingen, Germany.
⁹ Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
¹⁰ Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
¹¹ Intramural Research Program, National Institute of Mental Health, National Institutes of Health, US Dept of Health & Human Services, Bethesda, MD, USA.
¹² Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.
¹³ Max Planck Institute of Psychiatry, Munich, Germany.
¹⁴ Private Neuropathic Hospital Dr. med. Kurt Fontheim, Liebenburg, Germany.
¹⁵ Unit of Clinical Pharmacology, Hospital University Agency of Cagliari, Cagliari, Italy.
¹⁶ Departament Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Institut de Biomedicina de la Universitat de Barcelona (IBUB), CIBERSAM, Universitat de Barcelona, Barcelona, Spain.
¹⁷ Department of Psychiatry, University of Münster, Münster, Germany.
¹⁸ Mood Disorders Unit, Department of Psychiatry, HUG - Geneva University Hospitals, Geneva, Switzerland.
¹⁹ Department of Molecular Medicine and Surgery, Karolinska Institutet and The Centre for Psychiatric Research, Stockholm, Sweden.
²⁰ Department of Psychiatry and Psychotherapy, Carl Gustav Carus University Hospital, Technische Universität Dresden, Dresden, Germany.
²¹ Discipline of Psychiatry, Royal Adelaide Hospital, Adelaide School of Medical Schooline, The University of Adelaide, Adelaide, SA, Australia.
²² Department of Psychiatry II, Ulm University, Bezirkskrankenhaus Günzburg, Günzburg, Germany.
²³ INSERM UMR-S 1144 - Université Paris Diderot, Pôle de Psychiatrie, AP-HP, Groupe Hospitalier Lariboisière-F. Widal, Paris, France.
²⁴ Bipolar Disorders Program, Institute of Neurosciences, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain.
²⁵ Medical University of Graz, Graz, Austria.
²⁶ Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
²⁷ Mayo Clinic, Rochester, MN, USA.
²⁸ Mood Disorders Program, McGill University Health Centre, Montreal, QC, Canada.
²⁹ Mental Health Program, IMIM (Hospital del Mar Medical Research Institute), CIBERSAM Barcelona, Catolonia, Spain.
³⁰ Laboratory of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, Poland.
³¹ Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
³² Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
³³ AMEOS Clinical Center Hildesheim, Hildesheim, Germany.
³⁴ Department of Psychiatry and Psychotherapy, Neurophysiology & Interventional Neuropsychiatry, University of Tübingen, Tübingen, Germany.
³⁵ Karl-Jaspers Clinic, European Medical School Oldenburg-Groningen, Oldenburg, Germany.
³⁶ Department of Psychiatry, Psychotherapy and Psychosomatics, Clinical Center Wilhelmshaven, Wilhelmshaven, Germany.
³⁷ Neuroscience Research Australia, Sydney, NSW, Australia.
³⁸ School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
³⁹ CH Ch Perrens, Bordeaux, France.
⁴⁰ Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, Romania.
⁴¹ INSERM U955 Equipe 15 - Psychiatrie Genetique, Hopital Henri Mondor, Creteil, Cedex, France.
⁴² Department of Psychiatry, Ruhr University Bochum, LWL University Hospital, Bochum, Germany.
⁴³ Service de Psychiatrie et Psychologie Clinique, Centre Psychothérapique de Nancy - Université de Lorraine, Nancy, France.
⁴⁴ Human Genetics Branch, Section on Genetic Basis of Mood and Anxiety Disorders, National Institutes of Health, Bethesda, MD, USA.
⁴⁵ Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany.
⁴⁶ Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
⁴⁷ Asklepios Specialized Hospital, Göttingen, Germany.
⁴⁸ Hospital Neunkirchen, Neunkirchen, Germany.
⁴⁹ Department of Psychiatry and Psychotherapy, Agaplesion Diakonieklinikum, Rotenburg, Germany.
⁵⁰ Gothenburg University, Sahlgrenska Academy, Gothenburg, Sweden.
⁵¹ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁵² Assistance Publique-Hôpitaux de Paris, Hôpital Albert Chenevier - Henri Mondor, Pôle de Psychiatrie, Créteil, France.
⁵³ Department of Pharmacy, VA San Diego Healthcare System, San Diego, CA, USA.
⁵⁴ Department of Psychiatry, Campania University L. Vanvitelli, Naples, Italy.
⁵⁵ Section of Psychiatry, Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Cagliari, Italy.
⁵⁶ Department of Pharmacology, Dalhousie University, Halifax, NS, Canada.
⁵⁷ Department of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden.
⁵⁸ Lindner Center of HOPE, Research Institute, Mason, OH, USA.
⁵⁹ School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
⁶⁰ Black Dog Institute, Prince of Wales Hospital, Sydney, NSW, Australia.
⁶¹ Unitat d'Antropologia (Dp. Biología Animal), Department of Biologia Animal, Facultat de Biologia and Institut de Biomedicina (IBUB), Universitat de Barcelona, CIBERSAM, Barcelona, Spain.
⁶² Neurosciences Section, Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
⁶³ National Institute of Mental Health, Klecany, Czech Republic.
⁶⁴ Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
⁶⁵ Department of Psychiatry, Karolinska Institutet, Stockholm, Sweden.
⁶⁶ Psychiatry, University of Iowa, Iowa City, IA, USA.
⁶⁷ Department of Psychiatry, Klinikum Bremen-Ost, Bremen, Germany.
⁶⁸ Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA.
⁶⁹ AMEOS Clinical Center Osnabrück, Osnabrück, Germany.
⁷⁰ Department of Psychiatry and Psychotherapy, Bezirkskrankenhaus Augsburg, Augsburg, Germany.
⁷¹ Sigmund Freud University, Vienna, Austria.
⁷² Bipolar Zentrum, Wiener Neustadt, Austria.
⁷³ ASKLEPIOS Specialized Hospital Tiefenbrunn, Rosdorf, Germany.
⁷⁴ Department of Psychiatry, Psychotherapy and Psychosomatics, Medical School Brandenburg, Neuruppin, Germany.
⁷⁵ Psychiatric Hospital Lüneburg, Lüneburg, Germany.
⁷⁶ Department of Psychiatry, University of Perugia, Perugia, Italy.
⁷⁷ Douglas Hospital, Verdun, QC, Canada.
⁷⁸ Clinic for Psychiatry and Psychotherapy, Clinical Center Werra-Meißner, Eschwege, Germany.

PMID: 29956436
PMCID: PMC6585855
DOI: 10.1111/bdi.12659

Multicenter Study

Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study

Janos L Kalman et al. Bipolar Disord. 2019 Feb.

. 2019 Feb;21(1):68-75.

doi: 10.1111/bdi.12659. Epub 2018 Jun 28.

Authors

Affiliations

¹ Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany.
² Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Munich, Germany.
³ International Max Planck Research School for Translational Psychiatry (IMPRS-TP), Munich, Germany.
⁴ Instituto de Salud Carlos III, Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain.
⁵ Institute of Human Genetics, University of Bonn and Department of Genomics, Life & Brain Center, Bonn, Germany.
⁶ Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
⁷ Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland.
⁸ Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August University Göttingen, Göttingen, Germany.
⁹ Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
¹⁰ Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
¹¹ Intramural Research Program, National Institute of Mental Health, National Institutes of Health, US Dept of Health & Human Services, Bethesda, MD, USA.
¹² Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.
¹³ Max Planck Institute of Psychiatry, Munich, Germany.
¹⁴ Private Neuropathic Hospital Dr. med. Kurt Fontheim, Liebenburg, Germany.
¹⁵ Unit of Clinical Pharmacology, Hospital University Agency of Cagliari, Cagliari, Italy.
¹⁶ Departament Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Institut de Biomedicina de la Universitat de Barcelona (IBUB), CIBERSAM, Universitat de Barcelona, Barcelona, Spain.
¹⁷ Department of Psychiatry, University of Münster, Münster, Germany.
¹⁸ Mood Disorders Unit, Department of Psychiatry, HUG - Geneva University Hospitals, Geneva, Switzerland.
¹⁹ Department of Molecular Medicine and Surgery, Karolinska Institutet and The Centre for Psychiatric Research, Stockholm, Sweden.
²⁰ Department of Psychiatry and Psychotherapy, Carl Gustav Carus University Hospital, Technische Universität Dresden, Dresden, Germany.
²¹ Discipline of Psychiatry, Royal Adelaide Hospital, Adelaide School of Medical Schooline, The University of Adelaide, Adelaide, SA, Australia.
²² Department of Psychiatry II, Ulm University, Bezirkskrankenhaus Günzburg, Günzburg, Germany.
²³ INSERM UMR-S 1144 - Université Paris Diderot, Pôle de Psychiatrie, AP-HP, Groupe Hospitalier Lariboisière-F. Widal, Paris, France.
²⁴ Bipolar Disorders Program, Institute of Neurosciences, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain.
²⁵ Medical University of Graz, Graz, Austria.
²⁶ Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
²⁷ Mayo Clinic, Rochester, MN, USA.
²⁸ Mood Disorders Program, McGill University Health Centre, Montreal, QC, Canada.
²⁹ Mental Health Program, IMIM (Hospital del Mar Medical Research Institute), CIBERSAM Barcelona, Catolonia, Spain.
³⁰ Laboratory of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, Poland.
³¹ Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
³² Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
³³ AMEOS Clinical Center Hildesheim, Hildesheim, Germany.
³⁴ Department of Psychiatry and Psychotherapy, Neurophysiology & Interventional Neuropsychiatry, University of Tübingen, Tübingen, Germany.
³⁵ Karl-Jaspers Clinic, European Medical School Oldenburg-Groningen, Oldenburg, Germany.
³⁶ Department of Psychiatry, Psychotherapy and Psychosomatics, Clinical Center Wilhelmshaven, Wilhelmshaven, Germany.
³⁷ Neuroscience Research Australia, Sydney, NSW, Australia.
³⁸ School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
³⁹ CH Ch Perrens, Bordeaux, France.
⁴⁰ Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, Romania.
⁴¹ INSERM U955 Equipe 15 - Psychiatrie Genetique, Hopital Henri Mondor, Creteil, Cedex, France.
⁴² Department of Psychiatry, Ruhr University Bochum, LWL University Hospital, Bochum, Germany.
⁴³ Service de Psychiatrie et Psychologie Clinique, Centre Psychothérapique de Nancy - Université de Lorraine, Nancy, France.
⁴⁴ Human Genetics Branch, Section on Genetic Basis of Mood and Anxiety Disorders, National Institutes of Health, Bethesda, MD, USA.
⁴⁵ Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany.
⁴⁶ Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
⁴⁷ Asklepios Specialized Hospital, Göttingen, Germany.
⁴⁸ Hospital Neunkirchen, Neunkirchen, Germany.
⁴⁹ Department of Psychiatry and Psychotherapy, Agaplesion Diakonieklinikum, Rotenburg, Germany.
⁵⁰ Gothenburg University, Sahlgrenska Academy, Gothenburg, Sweden.
⁵¹ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁵² Assistance Publique-Hôpitaux de Paris, Hôpital Albert Chenevier - Henri Mondor, Pôle de Psychiatrie, Créteil, France.
⁵³ Department of Pharmacy, VA San Diego Healthcare System, San Diego, CA, USA.
⁵⁴ Department of Psychiatry, Campania University L. Vanvitelli, Naples, Italy.
⁵⁵ Section of Psychiatry, Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Cagliari, Italy.
⁵⁶ Department of Pharmacology, Dalhousie University, Halifax, NS, Canada.
⁵⁷ Department of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden.
⁵⁸ Lindner Center of HOPE, Research Institute, Mason, OH, USA.
⁵⁹ School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
⁶⁰ Black Dog Institute, Prince of Wales Hospital, Sydney, NSW, Australia.
⁶¹ Unitat d'Antropologia (Dp. Biología Animal), Department of Biologia Animal, Facultat de Biologia and Institut de Biomedicina (IBUB), Universitat de Barcelona, CIBERSAM, Barcelona, Spain.
⁶² Neurosciences Section, Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
⁶³ National Institute of Mental Health, Klecany, Czech Republic.
⁶⁴ Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
⁶⁵ Department of Psychiatry, Karolinska Institutet, Stockholm, Sweden.
⁶⁶ Psychiatry, University of Iowa, Iowa City, IA, USA.
⁶⁷ Department of Psychiatry, Klinikum Bremen-Ost, Bremen, Germany.
⁶⁸ Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA.
⁶⁹ AMEOS Clinical Center Osnabrück, Osnabrück, Germany.
⁷⁰ Department of Psychiatry and Psychotherapy, Bezirkskrankenhaus Augsburg, Augsburg, Germany.
⁷¹ Sigmund Freud University, Vienna, Austria.
⁷² Bipolar Zentrum, Wiener Neustadt, Austria.
⁷³ ASKLEPIOS Specialized Hospital Tiefenbrunn, Rosdorf, Germany.
⁷⁴ Department of Psychiatry, Psychotherapy and Psychosomatics, Medical School Brandenburg, Neuruppin, Germany.
⁷⁵ Psychiatric Hospital Lüneburg, Lüneburg, Germany.
⁷⁶ Department of Psychiatry, University of Perugia, Perugia, Italy.
⁷⁷ Douglas Hospital, Verdun, QC, Canada.
⁷⁸ Clinic for Psychiatry and Psychotherapy, Clinical Center Werra-Meißner, Eschwege, Germany.

PMID: 29956436
PMCID: PMC6585855
DOI: 10.1111/bdi.12659

Abstract

Objectives: Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients.

Methods: A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18 years] vs adulthood [>18 years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models.

Results: BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment.

Conclusions: The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.

Keywords: age at onset; bipolar disorder; early onset; polygenic risk score; schizophrenia.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. The funding agencies had no role in the design of the study; in the collection, analyses, or interpretation of data. Neither were they involved in the writing of the manuscript, or in the decision to publish the results.

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[1] Nöthen MM, Nieratschker V, Cichon S, Rietschel M. New findings in the genetics of major psychoses. Dialogues Clin Neurosci. 2010;12:85‐93. - PMC - PubMed

[2] Nöthen MM, Nieratschker V, Cichon S, Rietschel M. New findings in the genetics of major psychoses. Dialogues Clin Neurosci. 2010;12:85‐93. - PMC - PubMed

[3] Zheng J, Erzurumluoglu AM, Elsworth BL, et al. LD Hub: a centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis. Bioinformatics. 2017;33:272‐279. - PMC - PubMed

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Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study

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Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study

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