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

Journal article
Authors Janos L Kalman
Sergi Papiol
Andreas J Forstner
Urs Heilbronner
Franziska Degenhardt
Jana Strohmaier
Mazda Adli
Kristina Adorjan
Nirmala Akula
Martin Alda
Heike Anderson-Schmidt
Till Fm Andlauer
Ion-George Anghelescu
Raffaella Ardau
Bárbara Arias
Volker Arolt
Jean-Michel Aubry
Lena Backlund
Kim Bartholdi
Michael Bauer
Bernhard T Baune
Thomas Becker
Frank Bellivier
Antonio Benabarre
Susanne Bengesser
Abesh Kumar Bhattacharjee
Joanna M Biernacka
Armin Birner
Clara Brichant-Petitjean
Monika Budde
Pablo Cervantes
Caterina Chillotti
Sven Cichon
Scott R Clark
Francesc Colom
Ashley L Comes
Cristiana Cruceanu
Piotr M Czerski
Udo Dannlowski
Alexandre Dayer
Maria Del Zompo
Jay Raymond DePaulo
Detlef E Dietrich
Bruno Étain
Thomas Ethofer
Peter Falkai
Andreas Fallgatter
Christian Figge
Laura Flatau
Here Folkerts
Louise Frisen
Mark A Frye
Janice M Fullerton
Katrin Gade
Sébastien Gard
Julie S Garnham
Fernando S Goes
Maria Grigoroiu-Serbanescu
Anna Gryaznova
Maria Hake
Joanna Hauser
Stefan Herms
Per Hoffmann
Liping Hou
Markus Jäger
Stephane Jamain
Esther Jiménez
Georg Juckel
Jean-Pierre Kahn
Layla Kassem
John Kelsoe
Sarah Kittel-Schneider
Sebastian Kliwicki
Farah Klohn-Sagatholislam
Manfred Koller
Barbara König
Carsten Konrad
Nina Lackner
Gonzalo Laje
Mikael Landén
Fabian U Lang
Catharina Lavebratt
Marion Leboyer
Susan G Leckband
Mario Maj
Mirko Manchia
Lina Martinsson
Michael J McCarthy
Susan L McElroy
Francis J McMahon
Philip B Mitchell
Marina Mitjans
Francis M Mondimore
Palmiero Monteleone
Vanessa Nieratschker
Caroline M Nievergelt
Tomas Novák
Urban Ösby
Andrea Pfennig
James B Potash
Daniela Reich-Erkelenz
Andreas Reif
Jens Reimer
Eva Reininghaus
Markus Reitt
Stephan Ripke
Guy A Rouleau
Janusz K Rybakowski
Martin Schalling
Harald Scherk
Max Schmauß
Peter R Schofield
K Oliver Schubert
Eva C Schulte
Sybille Schulz
Fanny Senner
Giovanni Severino
Tatyana Shekhtman
Paul D Shilling
Christian Simhandl
Claire M Slaney
Carsten Spitzer
Alessio Squassina
Thomas Stamm
Sophia Stegmaier
Sebastian Stierl
Pavla Stopkova
Andreas Thiel
Sarah K Tighe
Alfonso Tortorella
Gustavo Turecki
Eduard Vieta
Julia Veeh
Martin von Hagen
Moritz E Wigand
Jens Wiltfang
Stephanie Witt
Adam Wright
Peter P Zandi
Jörg Zimmermann
Markus Nöthen
Marcella Rietschel
Thomas G Schulze
Published in Bipolar disorders
Volume 21
Issue 1
Pages 68-75
ISSN 1399-5618
Publication year 2019
Published at Institute of Neuroscience and Physiology
Pages 68-75
Language en
Links dx.doi.org/10.1111/bdi.12659
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Psychiatry

Abstract

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.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.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.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.

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