Characterisation of age and polarity at onset in bipolar disorder

Kalman JL, Loohuis LM, Vreeker A, McQuillin A, Stahl EA, Ruderfer D, Grigoroiu-Serbanescu M, Panagiotaropoulou G, Ripke S, Bigdeli TB, Stein F, Meller T, Meinert S, Pelin H, Streit F, Papiol S, Adams MJ, Adolfsson R, Adorjan K, Agartz I, Aminoff SR, Anderson-Schmidt H, Andreassen OA, Ardau R, Aubry JM, Balaban C, Bass N, Baune BT, Bellivier F, Benabarre A, Bengesser S, Berrettini WH, Boks MP, Bromet EJ, Brosch K, Budde M, Byerley W, Cervantes P, Chillotti C, Cichon S, Clark SR, Comes AL, Corvin A, Coryell W, Craddock N, Craig DW, Croarkin PE, Cruceanu C, Czerski PM, Dalkner N, Dannlowski U, Degenhardt F, Del Zompo M, Depaulo JR, Djurovic S, Edenberg HJ, Al Eissa M, Elvsåshagen T, Etain B, Fanous AH, Fellendorf F, Fiorentino A, Forstner AJ, Frye MA, Fullerton JM, Gade K, Garnham J, Gershon E, Gill M, Goes FS, Gordon-Smith K, Grof P, Guzman-Parra J, Hahn T, Hasler R, Heilbronner M, Heilbronner U, Jamain S, Jimenez E, Jones I, Jones L, Jonsson L, Kahn RS, Kelsoe JR, Kennedy JL, Kircher T, Kirov G, Kittel-Schneider S, Klöhn-Saghatolislam F, Knowles JA, Kranz TM, Lagerberg TV, Landen M, Lawson WB, Leboyer M, Li QS, Maj M, Malaspina D, Manchia M, Mayoral F, McElroy SL, McInnis MG, McIntosh AM, Medeiros H, Melle I, Milanova V, Mitchell PB, Monteleone P, Monteleone AM, Nöthen MM, Novak T, Nurnberger JI, O'Brien N, O'Connell KS, O'Donovan C, O'Donovan MC, Opel N, Ortiz A, Owen MJ, Pålsson E, Pato C, Pato MT, Pawlak J, Pfarr JK, Pisanu C, Potash JB, Rapaport MH, Reich-Erkelenz D, Reif A, Reininghaus E, Repple J, Richard-Lepouriel H, Rietschel M, Ringwald K, Roberts G, Rouleau G, Schaupp S, Scheftner WA, Schmitt S, Schofield PR, Schubert KO, Schulte EC, Schweizer B, Senner F, Severino G, Sharp S, Slaney C, Smeland OB, Sobell JL, Squassina A, Stopkova P, Strauss J, Tortorella A, Turecki G, Twarowska-Hauser J, Veldic M, Vieta E, Vincent JB, Xu W, Zai CC, Zandi PP, Di Florio A, Smoller JW, Biernacka JM, McMahon FJ, Alda M, Müller-Myhsok B, Koutsouleris N, Falkai P, Freimer NB, Andlauer TF, Schulze TG, Ophoff RA (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Book Volume: 219

Pages Range: 659-669

Journal Issue: 6

DOI: 10.1192/bjp.2021.102

Abstract

Background Studying 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. Aims To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics. Method Genome-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. Results Earlier 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. Conclusions AAO 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.

Involved external institutions

Klinikum der Universität München (LMU Klinikum) Germany (DE) Umeå University Sweden (SE) Medizinische Universität Graz Austria (AT) University of Pennsylvania (UPenn) United States (USA) (US) State University of New York at Albany (UNY Albany / UAlbany) United States (USA) (US) University of California San Francisco (UCSF) United States (USA) (US) Charité - Universitätsmedizin Berlin Germany (DE) University Of Worcester United Kingdom (GB) Mood Disorders Ottawa Canada (CA) University College London (UCL) United Kingdom (GB) Universitätsklinikum Bonn Germany (DE) Westfälische Wilhelms-Universität (WWU) Münster Germany (DE) SUNY Downstate Health Sciences University United States (USA) (US) Mayo Clinic United States (USA) (US) Neuroscience Research Australia NeuRA Australia (AU) Universitätsklinikum Göttingen Germany (DE) Paris-Est Créteil University / Université Paris-Est Créteil Val-de-Marne (UPEC) / Université Paris XII-Val-de-Marne / University Paris 12 Marne la Vallée France (FR) Universitat de Barcelona (UB) / University of Barcelona Spain (ES) Nova Scotia Health Canada (CA) Institut Mondor de Recherche Biomédicale France (FR) Icahn School of Medicine at Mount Sinai United States (USA) (US) Cardiff University United Kingdom (GB) Sahlgrenska University Hospital / Sahlgrenska Universitetssjukhuset Sweden (SE) Università degli Studi di Cagliari Italy (IT) University of Oslo Norway (NO) Dalhousie University Canada (CA) Geneva University Hospitals / Hôpitaux universitaires de Genève (HUG) Switzerland (CH) Ruprecht-Karls-Universität Heidelberg Germany (DE) Philipps-Universität Marburg Germany (DE) Universitätsklinikum Frankfurt am Main (KGU) Germany (DE) Howard University Hospital (HUH) / Freedmen's Hospital United States (USA) (US) The Jane and Terry Semel Institute for Neuroscience and Human Behavior United States (USA) (US) Janssen Global Services, LLC United States (USA) (US) Erasmus MC - Sophia Children’s Hospital Netherlands (NL) Università degli studi della Campania Luigi Vanvitelli Italy (IT) Lindner Center of HOPE United States (USA) (US) Vanderbilt University United States (USA) (US) University of Michigan United States (USA) (US) University of Edinburgh United Kingdom (GB) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) University of Toronto Canada (CA) University of New South Wales (UNSW) Australia (AU) Klinikum rechts der Isar Germany (DE) University of Adelaide Australia (AU) Johns Hopkins University (JHU) United States (USA) (US) University of Southern California (USC) United States (USA) (US) National Institute of Mental Health Information Resource Center United States (USA) (US) University Medical Centre Utrecht (UMC Utrecht) Netherlands (NL) Trinity College Dublin Ireland (IE) SUNY Downstate Medical Center United States (USA) (US) Università degli Studi di Salerno Italy (IT) Università degli Studi di Perugia Italy (IT) Poznan University of Medical Sciences / Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu Poland (PL) Indiana University – Purdue University Indianapolis United States (USA) (US) Emory University United States (USA) (US) King’s College London United Kingdom (GB) Harvard T.H. Chan School of Public Health United States (USA) (US) Eli and Edythe L. Broad Institute of MIT and Harvard United States (USA) (US) Max-Planck-Institut für Psychiatrie (Deutsche Forschungsanstalt für Psychiatrie) Germany (DE) Montreal Neurological Institute and Hospital (MNI, The Neuro) Canada (CA) Rush University United States (USA) (US) Hospital University Agency of Cagliari Italy (IT) Massachusetts General Hospital United States (USA) (US) Universität Basel Switzerland (CH) International Max Planck Research School for Translational Psychiatry (IMPRS-TP) Germany (DE) University of Iowa Hospitals and Clinics (UIHC) United States (USA) (US) Karolinska Institute Sweden (SE) Rheinische Friedrich-Wilhelms-Universität Bonn Germany (DE) Oslo University Hospital, Ullevål / Oslo universitetssykehus, Ullevål Norway (NO) Université Sorbonne Paris Cité France (FR) Assistance Publique-Hôpitaux de Paris (AP-HP) France (FR)

How to cite

APA:

Kalman, J.L., Loohuis, L.M., Vreeker, A., McQuillin, A., Stahl, E.A., Ruderfer, D.,... Ophoff, R.A. (2021). Characterisation of age and polarity at onset in bipolar disorder. British Journal of Psychiatry, 219(6), 659-669. https://doi.org/10.1192/bjp.2021.102

MLA:

Kalman, Janos L., et al. "Characterisation of age and polarity at onset in bipolar disorder." British Journal of Psychiatry 219.6 (2021): 659-669.

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