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

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

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Kalman, Janos L.1, Author           
Papiol, Sergi, Author
Forstner, Andreas J., Author
Heilbronner, Urs, Author
Degenhardt, Franziska, Author
Strohmaier, Jana, Author
Adli, Mazda, Author
Adorjan, Kristina, Author
Akula, Nirmala, Author
Alda, Martin, Author
Anderson-Schmidt, Heike, Author
Andlauer, Till F. M.2, Author           
Anghelescu, Ion-George, Author
Ardau, Raffaella, Author
Arias, Barbara, Author
Arolt, Volker, Author
Aubry, Jean-Michel, Author
Backlund, Lena, Author
Bartholdi, Kim, Author
Bauer, Michael, Author
Baune, Bernhard T., AuthorBecker, Thomas, AuthorBellivier, Frank, AuthorBenabarre, Antonio, AuthorBengesser, Susanne, AuthorBhattacharjee, Abesh Kumar, AuthorBiernacka, Joanna M., AuthorBirner, Armin, AuthorBrichant-Petitjean, Clara, AuthorBudde, Monika, AuthorCervantes, Pablo, AuthorChillotti, Caterina, AuthorCichon, Sven, AuthorClark, Scott R., AuthorColom, Francesc, AuthorComes, Ashley L., AuthorCruceanu, Cristiana2, Author           Czerski, Piotr M., AuthorDannlowski, Udo, AuthorDayer, Alexandre, AuthorDel Zompo, Maria, AuthorDePaulo, Jay Raymond, AuthorDietrich, Detlef E., AuthorEtain, Bruno, AuthorEthofer, Thomas, AuthorFalkai, Peter, AuthorFallgatter, Andreas, AuthorFigge, Christian, AuthorFlatau, Laura, AuthorFolkerts, Here, AuthorFrisen, Louise, AuthorFrye, Mark A., AuthorFullerton, Janice M., AuthorGade, Katrin, AuthorGard, Sebastien, AuthorGarnham, Julie S., AuthorGoes, Fernando S., AuthorGrigoroiu-Serbanescu, Maria, AuthorGryaznova, Anna, AuthorHake, Maria, AuthorHauser, Joanna, AuthorHerms, Stefan, AuthorHoffmann, Per, AuthorHou, Liping, AuthorJaeger, Markus, AuthorJamain, Stephane, AuthorJimenez, Esther, AuthorJuckel, Georg, AuthorKahn, Jean-Pierre, AuthorKassem, Layla, AuthorKelsoe, John, AuthorKittel-Schneider, Sarah, AuthorKliwicki, Sebastian, AuthorKlohn-Sagatholislam, Farah, AuthorKoller, Manfred, AuthorKoenig, Barbara, AuthorKonrad, Carsten, AuthorLackner, Nina, AuthorLaje, Gonzalo, AuthorLanden, Mikael, AuthorLang, Fabian U., AuthorLavebratt, Catharina, AuthorLeboyer, Marion, AuthorLeckband, Susan G., AuthorMaj, Mario, AuthorManchia, Mirko, AuthorMartinsson, Lina, AuthorMcCarthy, Michael J., AuthorMcElroy, Susan L., AuthorMcMahon, Francis J., AuthorMitchell, Philip B., AuthorMitjans, Marina, AuthorMondimore, Francis M., AuthorMonteleone, Palmiero, AuthorNieratschker, Vanessa, AuthorNievergelt, Caroline M., AuthorNovak, Tomas, AuthorOsby, Urban, AuthorPfennig, Andrea, AuthorPotash, James B., AuthorReich-Erkelenz, Daniela, AuthorReif, Andreas, AuthorReimer, Jens, AuthorReininghaus, Eva, AuthorReitt, Markus, AuthorRipke, Stephan, AuthorRouleau, Guy A., AuthorRybakowski, Janusz K., AuthorSchalling, Martin, AuthorScherk, Harald, AuthorSchmauss, Max, AuthorSchofield, Peter R., AuthorSchubert, K. Oliver, AuthorSchulte, Eva C., AuthorSchulz, Sybille, AuthorSenner, Fanny, AuthorSeverino, Giovanni, AuthorShekhtman, Tatyana, AuthorShilling, Paul D., AuthorSimhandl, Christian, AuthorSlaney, Claire M., AuthorSpitzer, Carsten, AuthorSquassina, Alessio, AuthorStamm, Thomas, AuthorStegmaier, Sophia, AuthorStierl, Sebastian, AuthorStopkova, Pavla, AuthorThiel, Andreas, AuthorTighe, Sarah K., AuthorTortorella, Alfonso, AuthorTurecki, Gustavo, AuthorVieta, Eduard, AuthorVeeh, Julia, Authorvon Hagen, Martin, AuthorWigand, Moritz E., AuthorWiltfang, Jens, AuthorWitt, Stephanie, AuthorWright, Adam, AuthorZandi, Peter P., AuthorZimmermann, Joerg, AuthorNoethen, Markus, AuthorRietschel, Marcella, AuthorSchulze, Thomas G., Author more..
Affiliations:
1IMPRS Translational Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society, ou_3318616              
2Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society, ou_2035295              

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 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.

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 Dates: 2019
 Publication Status: Published in print
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 Rev. Type: -
 Identifiers: ISI: 000459791000009
DOI: 10.1111/bdi.12659
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Title: BIPOLAR DISORDERS
Source Genre: Journal
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Pages: - Volume / Issue: 21 (1) Sequence Number: - Start / End Page: 68 - 75 Identifier: ISSN: 1398-5647