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

Kalman JL, Papiol S, Forstner AJ, Heilbronner U, Degenhardt F, Strohmaier J, Adli M, Adorjan K, Akula N, Alda M, Anderson-Schmidt H, Andlauer TF, Anghelescu IG, Ardau R, Arias B, Arolt V, Aubry JM, Backlund L, Bartholdi K, Bauer M, Baune BT, Becker T, Bellivier F, Benabarre A, Bengesser S, Bhattacharjee AK, Biernacka JM, Birner A, Brichant-Petitjean C, Budde M, Cervantes P, Chillotti C, Cichon S, Clark SR, Colom F, Comes AL, Cruceanu C, Czerski PM, Dannlowski U, Dayer A, Del Zompo M, DePaulo JR, Dietrich DE, Étain B, Ethofer T, Falkai P, Fallgatter A, Figge C, Flatau L, Folkerts H, Frisen L, Frye MA, Fullerton JM, Gade K, Gard S, Garnham JS, Goes FS, Grigoroiu-Serbanescu M, Gryaznova A, Hake M, Hauser J, Herms S, Hoffmann P, Hou L, Jäger M, Jamain S, Jiménez E, Juckel G, Kahn JP, Kassem L, Kelsoe J, Kittel-Schneider S, Kliwicki S, Klohn-Sagatholislam F, Koller M, König B, Konrad C, Lackner N, Laje G, Landén M, Lang FU, Lavebratt C, Leboyer M, Leckband SG, Maj M, Manchia M, Martinsson L, McCarthy MJ, McElroy SL, McMahon FJ, Mitchell PB, Mitjans M, Mondimore FM, Monteleone P, Nieratschker V, Nievergelt CM, Novák T, Ösby U, Pfennig A, Potash JB, Reich-Erkelenz D, Reif A, Reimer J, Reininghaus E, Reitt M, Ripke S, Rouleau GA, Rybakowski JK, Schalling M, Scherk H, Schmauß M, Schofield PR, Schubert KO, Schulte EC, Schulz S, Senner F, Severino G, Shekhtman T, Shilling PD, Simhandl C, Slaney CM, Spitzer C, Squassina A, Stamm T, Stegmaier S, Stierl S, Stopkova P, Thiel A, Tighe SK, Tortorella A, Turecki G, Vieta E, Veeh J, von Hagen M, Wigand ME, Wiltfang J, Witt S, Wright A, Zandi PP, Zimmermann J, Nöthen M, Rietschel M, Schulze TG (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Book Volume: 21

Pages Range: 68-75

Journal Issue: 1

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.

Authors with CRIS profile

Involved external institutions

Klinikum der Universität München (LMU Klinikum) Germany (DE) Rheinische Friedrich-Wilhelms-Universität Bonn Germany (DE) Ruprecht-Karls-Universität Heidelberg Germany (DE) Charité - Universitätsmedizin Berlin Germany (DE) National Institute of Mental Health Information Resource Center United States (USA) (US) Dalhousie University Canada (CA) Max-Planck-Institut für Psychiatrie (Deutsche Forschungsanstalt für Psychiatrie) Germany (DE) DR. FONTHEIM Mentale Gesundheit / Private Neuropathic Hospital Dr. med. Kurt Fontheim Germany (DE) Università degli Studi di Cagliari Italy (IT) Universitat de Barcelona (UB) / University of Barcelona Spain (ES) Universität Münster (ehem. Westfälische Wilhelms-Universität (WWU)) Germany (DE) Geneva University Hospitals / Hôpitaux universitaires de Genève (HUG) Switzerland (CH) Karolinska Institute Sweden (SE) Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) University of Adelaide Australia (AU) Universität Ulm Germany (DE) Université Paris Cité France (FR) Medizinische Universität Graz Austria (AT) Mayo Clinic United States (USA) (US) McGill University Health Centre (MUHC) / Centre universitaire de santé McGill Canada (CA) Poznan University of Medical Sciences / Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu Poland (PL) Johns Hopkins University (JHU) United States (USA) (US) AMEOS Klinikum Hildesheim Germany (DE) Universitätsklinikum Tübingen Germany (DE) Klinikum Wilhelmshaven gGmbH Germany (DE) Neuroscience Research Australia NeuRA Australia (AU) Centre Hospitalier Charles Perrens (CHCP) France (FR) Centre hospitalier universitaire Henri-Mondor (CHU Henri-Mondor) France (FR) Ruhr-Universität Bochum (RUB) Germany (DE) Université de Lorraine France (FR) US National Institutes of Health (NIH) United States (USA) (US) Städtisches Klinikum Lüneburg Germany (DE) Karl-Jaspers-Klinik Germany (DE) Universitätsklinikum Frankfurt am Main (KGU) Germany (DE) Asklepios Kliniken Germany (DE) Stiftung Kreuznacher Diakonie Germany (DE) Agaplesion Diakonieklinikum Rotenburg Germany (DE) Sahlgrenska University Hospital / Sahlgrenska Universitetssjukhuset Sweden (SE) VA San Diego Healthcare System United States (USA) (US) Università degli studi della Campania Luigi Vanvitelli Italy (IT) Lindner Center of HOPE United States (USA) (US) University of New South Wales (UNSW) Australia (AU) National Institute of Mental Health (NIMH) / Národní ústav duševního zdraví (NUDZ) Czech Republic (CZ) University of Iowa United States (USA) (US) Klinikum Bremen-Ost Germany (DE) Universitätsklinikum Göttingen Germany (DE) AMEOS Klinik Osnabrück Germany (DE) Bezirkskliniken Schwaben Germany (DE) Sigmund-Freud-Privatuniversität Wien (SFU) / Sigmund Freud University Austria (AT) Università degli Studi di Perugia Italy (IT) Douglas Mental Health University Institute Canada (CA) Klinikum Werra-Meißner / Clinical Center Werra-Meißner Germany (DE)

How to cite

APA:

Kalman, J.L., Papiol, S., Forstner, A.J., Heilbronner, U., Degenhardt, F., Strohmaier, J.,... Schulze, T.G. (2019). Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study. Bipolar Disorders, 21(1), 68-75. https://doi.org/10.1111/bdi.12659

MLA:

Kalman, Janos L., et al. "Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study." Bipolar Disorders 21.1 (2019): 68-75.

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