TY - JOUR
T1 - Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study.
JF - Bipolar Disord
Y1 - 2018
A1 - Kalman, Janos L
A1 - Papiol, Sergi
A1 - Forstner, Andreas J
A1 - Heilbronner, Urs
A1 - Degenhardt, Franziska
A1 - Strohmaier, Jana
A1 - Adli, Mazda
A1 - Adorjan, Kristina
A1 - Akula, Nirmala
A1 - Alda, Martin
A1 - Anderson-Schmidt, Heike
A1 - Andlauer, Till Fm
A1 - Anghelescu, Ion-George
A1 - Ardau, Raffaella
A1 - Arias, Bárbara
A1 - Arolt, Volker
A1 - Aubry, Jean-Michel
A1 - Backlund, Lena
A1 - Bartholdi, Kim
A1 - Bauer, Michael
A1 - Baune, Bernhard T
A1 - Becker, Thomas
A1 - Bellivier, Frank
A1 - Benabarre, Antonio
A1 - Bengesser, Susanne
A1 - Bhattacharjee, Abesh Kumar
A1 - Biernacka, Joanna M
A1 - Birner, Armin
A1 - Brichant-Petitjean, Clara
A1 - Budde, Monika
A1 - Cervantes, Pablo
A1 - Chillotti, Caterina
A1 - Cichon, Sven
A1 - Clark, Scott R
A1 - Colom, Francesc
A1 - Comes, Ashley L
A1 - Cruceanu, Cristiana
A1 - Czerski, Piotr M
A1 - Dannlowski, Udo
A1 - Dayer, Alexandre
A1 - Del Zompo, Maria
A1 - DePaulo, Jay Raymond
A1 - Dietrich, Detlef E
A1 - Étain, Bruno
A1 - Ethofer, Thomas
A1 - Falkai, Peter
A1 - Fallgatter, Andreas
A1 - Figge, Christian
A1 - Flatau, Laura
A1 - Folkerts, Here
A1 - Frisén, Louise
A1 - Frye, Mark A
A1 - Fullerton, Janice M
A1 - Gade, Katrin
A1 - Gard, Sébastien
A1 - Garnham, Julie S
A1 - Goes, Fernando S
A1 - Grigoroiu-Serbanescu, Maria
A1 - Gryaznova, Anna
A1 - Hake, Maria
A1 - Hauser, Joanna
A1 - Herms, Stefan
A1 - Hoffmann, Per
A1 - Hou, Liping
A1 - Jäger, Markus
A1 - Jamain, Stephane
A1 - Jiménez, Esther
A1 - Juckel, Georg
A1 - Kahn, Jean-Pierre
A1 - Kassem, Layla
A1 - Kelsoe, John
A1 - Kittel-Schneider, Sarah
A1 - Kliwicki, Sebastian
A1 - Klohn-Sagatholislam, Farah
A1 - Koller, Manfred
A1 - König, Barbara
A1 - Konrad, Carsten
A1 - Lackner, Nina
A1 - Laje, Gonzalo
A1 - Landen, Mikael
A1 - Lang, Fabian U
A1 - Lavebratt, Catharina
A1 - Leboyer, Marion
A1 - Leckband, Susan G
A1 - Maj, Mario
A1 - Manchia, Mirko
A1 - Martinsson, Lina
A1 - McCarthy, Michael J
A1 - McElroy, Susan L
A1 - McMahon, Francis J
A1 - Mitchell, Philip B
A1 - Mitjans, Marina
A1 - Mondimore, Francis M
A1 - Monteleone, Palmiero
A1 - Nieratschker, Vanessa
A1 - Nievergelt, Caroline M
A1 - Novák, Tomas
A1 - Ösby, Urban
A1 - Pfennig, Andrea
A1 - Potash, James B
A1 - Reich-Erkelenz, Daniela
A1 - Reif, Andreas
A1 - Reimer, Jens
A1 - Reininghaus, Eva
A1 - Reitt, Markus
A1 - Ripke, Stephan
A1 - Rouleau, Guy A
A1 - Rybakowski, Janusz K
A1 - Schalling, Martin
A1 - Scherk, Harald
A1 - Schmauß, Max
A1 - Schofield, Peter R
A1 - Schubert, K Oliver
A1 - Schulte, Eva C
A1 - Schulz, Sybille
A1 - Senner, Fanny
A1 - Severino, Giovanni
A1 - Shekhtman, Tatyana
A1 - Shilling, Paul D
A1 - Simhandl, Christian
A1 - Slaney, Claire M
A1 - Spitzer, Carsten
A1 - Squassina, Alessio
A1 - Stamm, Thomas
A1 - Stegmaier, Sophia
A1 - Stierl, Sebastian
A1 - Stopkova, Pavla
A1 - Thiel, Andreas
A1 - Tighe, Sarah K
A1 - Tortorella, Alfonso
A1 - Gustavo Turecki
A1 - Vieta, Eduard
A1 - Veeh, Julia
A1 - von Hagen, Martin
A1 - Wigand, Moritz E
A1 - Wiltfang, Jens
A1 - Witt, Stephanie
A1 - Wright, Adam
A1 - Zandi, Peter P
A1 - Zimmermann, Jörg
A1 - Nöthen, Markus
A1 - Rietschel, Marcella
A1 - Schulze, Thomas G
AB - **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.

U1 - http://www.ncbi.nlm.nih.gov/pubmed/29956436?dopt=Abstract
ER -