1. Characterisation of age and polarity at onset in bipolar disorder
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Kalman, Janos, Olde Loohuis, Loes, Vreeker, Annabel, Mcquillin, Andrew, Stahl, Eli, Ruderfer, Douglas, Grigoroiu-Serbanescu, Maria, Panagiotaropoulou, Georgia, Ripke, Stephan, Bigdeli, Tim, Stein, Frederike, Meller, Tina, Meinert, Susanne, Pelin, Helena, Streit, Fabian, Papiol, Sergi, Adams, Mark, Adolfsson, Rolf, Adorjan, Kristina, Agartz, Ingrid, Aminoff, Sofie, Anderson-Schmidt, Heike, Andreassen, Ole, Ardau, Raffaella, Aubry, Jean-Michel, Balaban, Ceylan, Bass, Nicholas, Baune, Bernhard, Bellivier, Frank, Benabarre, Antoni, Bengesser, Susanne, Berrettini, Wade, Boks, Marco, Bromet, Evelyn, Brosch, Katharina, Budde, Monika, Byerley, William, Cervantes, Pablo, Chillotti, Catina, Cichon, Sven, Clark, Scott, Comes, Ashley, Corvin, Aiden, Coryell, William, Craddock, Nick, Craig, David, Croarkin, Paul, Cruceanu, Cristiana, Czerski, Piotr, Dalkner, Nina, Dannlowski, Udo, Degenhardt, Franziska, del Zompo, Maria, Depaulo, J Raymond, Djurovic, Srdjan, Edenberg, Howard, Eissa, Mariam Al, Elvsåshagen, Torbjørn, Etain, Bruno, Fanous, Ayman, Fellendorf, Frederike, Fiorentino, Alessia, Forstner, Andreas, Frye, Mark, Fullerton, Janice, Gade, Katrin, Garnham, Julie, Gershon, Elliot, Gill, Michael, Goes, Fernando, Gordon-Smith, Katherine, Grof, Paul, Guzman-Parra, Jose, Hahn, Tim, Hasler, Roland, Heilbronner, Maria, Heilbronner, Urs, Jamain, Stephane, Jimenez, Esther, Jones, Ian, Jones, Lisa, Jonsson, Lina, Kahn, Rene, Kelsoe, John, Kennedy, James, Kircher, Tilo, Kirov, George, Kittel-Schneider, Sarah, Klöhn-Saghatolislam, Farah, Knowles, James, Kranz, Thorsten, Lagerberg, Trine Vik, Landen, Mikael, Lawson, William, Leboyer, Marion, Li, Qingqin, Maj, Mario, Malaspina, Dolores, Manchia, Mirko, Mayoral, Fermin, Mcelroy, Susan, Mcinnis, Melvin, McIntosh, Andrew, Medeiros, Helena, Melle, Ingrid, Milanova, Vihra, Mitchell, Philip, Monteleone, Palmiero, Monteleone, Alessio Maria, Nöthen, Markus, Novak, Tomas, Nurnberger, John, O'Brien, Niamh, O'Connell, Kevin, O'Donovan, Claire, O'Donovan, Michael, Opel, Nils, Ortiz, Abigail, Owen, Michael, Pålsson, Erik, Pato, Carlos, Pato, Michele, Pawlak, Joanna, Pfarr, Julia-Katharina, Pisanu, Claudia, Potash, James, Rapaport, Mark, Reich-Erkelenz, Daniela, Reif, Andreas, Reininghaus, Eva, Repple, Jonathan, Richard-Lepouriel, Hélène, Rietschel, Marcella, Ringwald, Kai, Roberts, Gloria, Rouleau, Guy, Schaupp, Sabrina, Scheftner, William, Schmitt, Simon, Schofield, Peter, Schubert, K Oliver, Schulte, Eva, Schweizer, Barbara, Senner, Fanny, Severino, Giovanni, Sharp, Sally, Slaney, Claire, Smeland, Olav, Sobell, Janet, Squassina, Alessio, Stopkova, Pavla, Strauss, John, Tortorella, Alfonso, Turecki, Gustavo, Twarowska-Hauser, Joanna, Veldic, Marin, Vieta, Eduard, Vincent, John, Xu, Wei, Zai, Clement, Zandi, Peter, Di Florio, Arianna, Smoller, Jordan, Biernacka, Joanna, Mcmahon, Francis, Alda, Martin, Müller-Myhsok, Bertram, Koutsouleris, Nikolaos, Falkai, Peter, Freimer, Nelson, Andlauer, Till, Schulze, Thomas, Ophoff, Roel, Depaulo, J. Raymond, Schubert, K. Oliver, Andlauer, Till F.M., Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Etain, Bruno, Child and Adolescent Psychiatry / Psychology, Psychiatry, Kalman, J. L., Loohuis, L. M. O., Vreeker, A., Mcquillin, A., Stahl, E. A., Ruderfer, D., Grigoroiu-Serbanescu, M., Panagiotaropoulou, G., Ripke, S., Bigdeli, T. B., Stein, F., Meller, T., Meinert, S., Pelin, H., Streit, F., Papiol, S., Adams, M. J., Adolfsson, R., Adorjan, K., Agartz, I., Aminoff, S. R., Anderson-Schmidt, H., Andreassen, O. A., Ardau, R., Aubry, J. -M., Balaban, C., Bass, N., Baune, B. T., Bellivier, F., Benabarre, A., Bengesser, S., Berrettini, W. H., Boks, M. P., Bromet, E. J., Brosch, K., Budde, M., Byerley, W., Cervantes, P., Chillotti, C., Cichon, S., Clark, S. R., Comes, A. L., Corvin, A., Coryell, W., Craddock, N., Craig, D. W., Croarkin, P. E., Cruceanu, C., Czerski, P. M., Dalkner, N., Dannlowski, U., Degenhardt, F., Del Zompo, M., Depaulo, J. R., Djurovic, S., Edenberg, H. J., Al Eissa, M., Elvsashagen, T., Etain, B., Fanous, A. H., Fellendorf, F., Fiorentino, A., Forstner, A. J., Frye, M. A., Fullerton, J. M., Gade, K., Garnham, J., Gershon, E., Gill, M., Goes, F. S., 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, R. S., Kelsoe, J. R., Kennedy, J. L., Kircher, T., Kirov, G., Kittel-Schneider, S., Klohn-Saghatolislam, F., Knowles, J. A., Kranz, T. M., Lagerberg, T. V., Landen, M., Lawson, W. B., Leboyer, M., Li, Q. S., Maj, M., Malaspina, D., Manchia, M., Mayoral, F., Mcelroy, S. L., Mcinnis, M. G., Mcintosh, A. M., Medeiros, H., Melle, I., Milanova, V., Mitchell, P. B., Monteleone, P., Monteleone, A. M., Nothen, M. M., Novak, T., Nurnberger, J. I., O'Brien, N., O'Connell, K. S., O'Donovan, C., O'Donovan, M. C., Opel, N., Ortiz, A., Owen, M. J., Palsson, E., Pato, C., Pato, M. T., Pawlak, J., Pfarr, J. -K., Pisanu, C., Potash, J. B., Rapaport, M. H., Reich-Erkelenz, D., Reif, A., Reininghaus, E., Repple, J., Richard-Lepouriel, H., Rietschel, M., Ringwald, K., Roberts, G., Rouleau, G., Schaupp, S., Scheftner, W. A., Schmitt, S., Schofield, P. R., Schubert, K. O., Schulte, E. C., Schweizer, B., Senner, F., Severino, G., Sharp, S., Slaney, C., Smeland, O. B., Sobell, J. L., Squassina, A., Stopkova, P., Strauss, J., Tortorella, A., Turecki, G., Twarowska-Hauser, J., Veldic, M., Vieta, E., Vincent, J. B., Xu, W., Zai, C. C., Zandi, P. P., Di Florio, A., Smoller, J. W., Biernacka, J. M., Mcmahon, F. J., Alda, M., Muller-Myhsok, B., Koutsouleris, N., Falkai, P., Freimer, N. B., Andlauer, T. F. M., Schulze, T. G., and Ophoff, R. A.
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Paper ,Multifactorial Inheritance ,medicine.medical_specialty ,Autism Spectrum Disorder ,Bipolar disorder ,MESH: Age of Onset ,[SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health ,Medizin ,GWAS ,age at onset ,polarity at onset ,polygenic score ,MESH: Depressive Disorder, Major ,BF ,Genome-wide association study ,Disease ,Psykiatri ,SDG 3 - Good Health and Well-being ,ddc:150 ,Polarity at onset ,Internal medicine ,MESH: Bipolar Disorder ,Polygenic score ,medicine ,Humans ,Academic Psychiatry ,Age of Onset ,Genetic association ,Psychiatry ,MESH: Autism Spectrum Disorder ,Depressive Disorder, Major ,MESH: Humans ,business.industry ,Age at onset ,Heritability ,medicine.disease ,Genetic architecture ,ddc ,Psychiatry and Mental health ,Schizophrenia ,Autism spectrum disorder ,[SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health ,MESH: Genome-Wide Association Study ,RC0321 ,MESH: Multifactorial Inheritance ,business ,Genome-Wide Association Study - Abstract
BackgroundStudying 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.AimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.MethodGenome-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.ResultsEarlier 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.ConclusionsAAO 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.
- Published
- 2021
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