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  Characterisation of age and polarity at onset in bipolar disorder

Kalman, J. L., Loohuis, L. M. O., Vreeker, A., McQuillin, A., Stahl, E. A., Ruderfer, D., et al. (2021). Characterisation of age and polarity at onset in bipolar disorder. BRITISH JOURNAL OF PSYCHIATRY, 219(6): PII S0007125021001021, pp. 659-669. doi:10.1192/bjp.2021.102.

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Kalman, Janos L.1, Autor           
Loohuis, Loes M. Olde, Autor
Vreeker, Annabel, Autor
McQuillin, Andrew, Autor
Stahl, Eli A., Autor
Ruderfer, Douglas, Autor
Grigoroiu-Serbanescu, Maria, Autor
Panagiotaropoulou, Georgia, Autor
Ripke, Stephan, Autor
Bigdeli, Tim B., Autor
Stein, Frederike, Autor
Meller, Tina, Autor
Meinert, Susanne, Autor
Pelin, Helena1, 2, Autor           
Streit, Fabian, Autor
Papiol, Sergi, Autor
Adams, Mark J., Autor
Adolfsson, Rolf, Autor
Adorjan, Kristina, Autor
Agartz, Ingrid, Autor
Aminoff, Sofie R., AutorAnderson-Schmidt, Heike, AutorAndreassen, Ole A., AutorArdau, Raffaella, AutorAubry, Jean-Michel, AutorBalaban, Ceylan, AutorBass, Nicholas, AutorBaune, Bernhard T., AutorBellivier, Frank, AutorBenabarre, Antoni, AutorBengesser, Susanne, AutorBerrettini, Wade H., AutorBoks, Marco P., AutorBromet, Evelyn J., AutorBrosch, Katharina, AutorBudde, Monika, AutorByerley, William, AutorCervantes, Pablo, AutorChillotti, Catina, AutorCichon, Sven, AutorClark, Scott R., AutorComes, Ashley L., AutorCorvin, Aiden, AutorCoryell, William, AutorCraddock, Nick, AutorCraig, David W., AutorCroarkin, Paul E., AutorCruceanu, Cristiana3, Autor           Czerski, Piotr M., AutorDalkner, Nina, AutorDannlowski, Udo, AutorDegenhardt, Franziska, AutorDel Zompo, Maria, AutorDePaulo, J. Raymond, AutorDjurovic, Srdjan, AutorEdenberg, Howard J., AutorAl Eissa, Mariam, AutorElvsashagen, Torbjorn, AutorEtain, Bruno, AutorFanous, Ayman H., AutorFellendorf, Frederike, AutorFiorentino, Alessia, AutorForstner, Andreas J., AutorFrye, Mark A., AutorFullerton, Janice M., AutorGade, Katrin, AutorGarnham, Julie, AutorGershon, Elliot, AutorGill, Michael, AutorGoes, Fernando S., AutorGordon-Smith, Katherine, AutorGrof, Paul, AutorGuzman-Parra, Jose, AutorHahn, Tim, AutorHasler, Roland, AutorHeilbronner, Maria, AutorHeilbronner, Urs, AutorJamain, Stephane, AutorJimenez, Esther, AutorJones, Ian, AutorJones, Lisa, AutorJonsson, Lina, AutorKahn, Rene S., AutorKelsoe, John R., AutorKennedy, James L., AutorKircher, Tilo, AutorKirov, George, AutorKittel-Schneider, Sarah, AutorKlohn-Saghatolislam, Farah, AutorKnowles, James A., AutorKranz, Thorsten M., AutorLagerberg, Trine Vik, AutorLanden, Mikael, AutorLawson, William B., AutorLeboyer, Marion, AutorLi, Qingqin S., AutorMaj, Mario, AutorMalaspina, Dolores, AutorManchia, Mirko, AutorMayoral, Fermin, AutorMcElroy, Susan L., AutorMcInnis, Melvin G., AutorMcIntosh, Andrew M., AutorMedeiros, Helena, AutorMelle, Ingrid, AutorMilanova, Vihra, AutorMitchell, Philip B., AutorMonteleone, Palmiero, AutorMonteleone, Alessio Maria, AutorNothen, Markus M., AutorNovak, Tomas, AutorNurnberger I, John, AutorO'Brien, Niamh, AutorO'Connell, Kevin S., AutorO'Donovan, Claire, AutorO'Donovan, Michael C., AutorOpel, Nils, AutorOrtiz, Abigail, AutorOwen, Michael J., AutorPalsson, Erik, AutorPato, Carlos, AutorPato, Michele T., AutorPawlak, Joanna, AutorPfarr, Julia-Katharina, AutorPisanu, Claudia, AutorPotash, James B., AutorRapaport, Mark H., AutorReich-Erkelenz, Daniela, AutorReif, Andreas, AutorReininghaus, Eva, AutorRepple, Jonathan, AutorRichard-Lepouriel, Helene, AutorRietschel, Marcella, AutorRingwald, Kai, AutorRoberts, Gloria, AutorRouleau, Guy, AutorSchaupp, Sabrina, AutorScheftner, William A., AutorSchmitt, Simon, AutorSchofield, Peter R., AutorSchubert, K. Oliver, AutorSchulte, Eva C., AutorSchweizer, Barbara, AutorSenner, Fanny, AutorSeverino, Giovanni, AutorSharp, Sally, AutorSlaney, Claire, AutorSmeland, Olav B., AutorSobell, Janet L., AutorSquassina, Alessio, AutorStopkova, Pavla, AutorStrauss, John, AutorTortorella, Alfonso, AutorTurecki, Gustavo, AutorTwarowska-Hauser, Joanna, AutorVeldic, Marin, AutorVieta, Eduard, AutorVincent, John B., AutorXu, Wei, AutorZai, Clement C., AutorZandi, Peter P., AutorDi Florio, Arianna, AutorSmoller, Jordan W., AutorBiernacka, Joanna M., AutorMcMahon, Francis J., AutorAlda, Martin, AutorMuller-Myhsok, Bertram2, Autor           Koutsouleris, Nikolaos4, Autor           Falkai, Peter, AutorFreimer, Nelson B., AutorAndlauer, Till F. M., AutorSchulze, Thomas G., AutorOphoff, Roel A., Autor mehr..
Affiliations:
1IMPRS Translational Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society, ou_3318616              
2RG Statistical Genetics, Max Planck Institute of Psychiatry, Max Planck Society, ou_2040288              
3Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society, ou_2035295              
4Max Planck Fellow Group Precision Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society, ou_3318615              

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 Zusammenfassung: 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 (beta = -0.34 years, s.e. = 0.08), major depression (beta = -0.34 years, s.e. = 0.08), schizophrenia (beta = -0.39 years, s.e. = 0.08), and educational attainment (beta = -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.

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 Datum: 2021
 Publikationsstatus: Online veröffentlicht
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 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: -
 Identifikatoren: ISI: 000723150400009
DOI: 10.1192/bjp.2021.102
 Art des Abschluß: -

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Titel: BRITISH JOURNAL OF PSYCHIATRY
Genre der Quelle: Zeitschrift
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Affiliations:
Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 219 (6) Artikelnummer: PII S0007125021001021 Start- / Endseite: 659 - 669 Identifikator: ISSN: 0007-1250