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Characterisation of age and polarity at onset in bipolar disorder
- Janos L. Kalman, Loes M. Olde Loohuis, Annabel Vreeker, Andrew McQuillin, Eli A. Stahl, Douglas Ruderfer, Maria Grigoroiu-Serbanescu, Georgia Panagiotaropoulou, Stephan Ripke, Tim B. Bigdeli, Frederike Stein, Tina Meller, Susanne Meinert, Helena Pelin, Fabian Streit, Sergi Papiol, Mark J. Adams, Rolf Adolfsson, Kristina Adorjan, Ingrid Agartz, Sofie R. Aminoff, Heike Anderson-Schmidt, Ole A. Andreassen, Raffaella Ardau, Jean-Michel Aubry, Ceylan Balaban, Nicholas Bass, Bernhard T. Baune, Frank Bellivier, Antoni Benabarre, Susanne Bengesser, Wade H Berrettini, Marco P. Boks, Evelyn J. Bromet, Katharina Brosch, Monika Budde, William Byerley, Pablo Cervantes, Catina Chillotti, Sven Cichon, Scott R. Clark, Ashley L. Comes, Aiden Corvin, William Coryell, Nick Craddock, David W. Craig, Paul E. Croarkin, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Udo Dannlowski, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Srdjan Djurovic, Howard J. Edenberg, Mariam Al Eissa, Torbjørn Elvsåshagen, Bruno Etain, Ayman H. Fanous, Frederike Fellendorf, Alessia Fiorentino, Andreas J. Forstner, Mark A. Frye, Janice M. Fullerton, Katrin Gade, Julie Garnham, Elliot Gershon, Michael Gill, Fernando S. Goes, Katherine Gordon-Smith, Paul Grof, Jose Guzman-Parra, Tim Hahn, Roland Hasler, Maria Heilbronner, Urs Heilbronner, Stephane Jamain, Esther Jimenez, Ian Jones, Lisa Jones, Lina Jonsson, Rene S. Kahn, John R. Kelsoe, James L. Kennedy, Tilo Kircher, George Kirov, Sarah Kittel-Schneider, Farah Klöhn-Saghatolislam, James A. Knowles, Thorsten M. Kranz, Trine Vik Lagerberg, Mikael Landen, William B. Lawson, Marion Leboyer, Qingqin S. Li, Mario Maj, Dolores Malaspina, Mirko Manchia, Fermin Mayoral, Susan L. McElroy, Melvin G. McInnis, Andrew M. McIntosh, Helena Medeiros, Ingrid Melle, Vihra Milanova, Philip B. Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Markus M. Nöthen, Tomas Novak, John I. Nurnberger, Niamh O'Brien, Kevin S. O'Connell, Claire O'Donovan, Michael C. O'Donovan, Nils Opel, Abigail Ortiz, Michael J. Owen, Erik Pålsson, Carlos Pato, Michele T. Pato, Joanna Pawlak, Julia-Katharina Pfarr, Claudia Pisanu, James B. Potash, Mark H Rapaport, Daniela Reich-Erkelenz, Andreas Reif, Eva Reininghaus, Jonathan Repple, Hélène Richard-Lepouriel, Marcella Rietschel, Kai Ringwald, Gloria Roberts, Guy Rouleau, Sabrina Schaupp, William A Scheftner, Simon Schmitt, Peter R. Schofield, K. Oliver Schubert, Eva C. Schulte, Barbara Schweizer, Fanny Senner, Giovanni Severino, Sally Sharp, Claire Slaney, Olav B. Smeland, Janet L. Sobell, Alessio Squassina, Pavla Stopkova, John Strauss, Alfonso Tortorella, Gustavo Turecki, Joanna Twarowska-Hauser, Marin Veldic, Eduard Vieta, John B. Vincent, Wei Xu, Clement C. Zai, Peter P. Zandi, Psychiatric Genomics Consortium (PGC) Bipolar Disorder Working Group, International Consortium on Lithium Genetics (ConLiGen), Colombia-US Cross Disorder Collaboration in Psychiatric Genetics, Arianna Di Florio, Jordan W. Smoller, Joanna M. Biernacka, Francis J. McMahon, Martin Alda, Bertram Müller-Myhsok, Nikolaos Koutsouleris, Peter Falkai, Nelson B. Freimer, Till F.M. Andlauer, Thomas G. Schulze, Roel A. Ophoff
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- Journal:
- The British Journal of Psychiatry / Volume 219 / Issue 6 / December 2021
- Published online by Cambridge University Press:
- 25 August 2021, pp. 659-669
- Print publication:
- December 2021
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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.
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.
Contributors
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- By Maricela Alarcón, Laura A. Baker, Trygve Bakken, Serena Bezdjian, Andrew W. Bergen, Laura J. Bierut, Andrew C. Chen, C. Robert Cloninger, David W. Craig, Anibal Cravchik, Raymond R. Crowe, Carlos Cruchaga, Joseph F. Cubells, Marcella Devoto, Stephen H. Dinwiddie, Howard J. Edenberg, Josephine Elia, Craig A. Erickson, Thomas V. Fernandez, Xiaowu Gai, Elliot Gershon, Daniel H. Geschwind, Alison M. Goate, Hugh M. D. Gurling, Hakon Hakonarson, Sarah M. Hartz, Akiko Hayashi-Takagi, Jinger Hoop, Hanna Jaaro-Peled, Atsushi Kamiya, John S. K. Kauwe, Walter H. Kaye, John R. Kelsoe, Karestan C. Koenen, Mary Jeanne Kreek, Francesca Lantieri, James F. Leckman, Ondrej Libiger, Falk W. Lohoff, Michael J. Lyons, Christopher J. McDougle, Andrew McQuillin, Kathleen Ries Merikangas, Maria G. Motlagh, Pablo R. Moya, Dennis L. Murphy, Eric J. Nestler, Alexander B. Niculescu, David A. Nielsen, Khendra I. Peay, Bernice Porjesz, James B. Potash, R. Arlen Price, Dmitri Proudnikov, Adrian Raine, Madhavi Rangaswamy, William Renthal, Akira Sawa, Nicholas J. Schork, Saurav Seshadri, Shelley D. Smith, Wanli W. Smith, Toshinobu Takeda, Ardesheer Talati, Yi-Lang Tang, Kiara Timpano, Ali Torkamani, Catherine Tuvblad, Myrna M. Weissman, Jens R. Wendland, Jennifer Wessel, Peter S. White, Vadim Yuferov, Tyler Zink
- Edited by John I. Nurnberger, Jr, Wade Berrettini, University of Pennsylvania School of Medicine
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- Book:
- Principles of Psychiatric Genetics
- Published online:
- 05 October 2012
- Print publication:
- 13 September 2012, pp vii-x
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Milliarcsecond Polarization Measurements
- David H. Roberts, Robert I. Potash, John F. C. Wardle, Alan E. E. Rogers, Bernard F. Burke
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- Journal:
- Symposium - International Astronomical Union / Volume 110 / 1984
- Published online by Cambridge University Press:
- 04 August 2017, pp. 35-38
- Print publication:
- 1984
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Linear polarization measurements at milliarcsecond resolution have been made at λ6 cm using four stations of the U. S. VLBI Network and the Mark III recording system. Calibration of the cross-polarization contamination of the feeds was done using the cross- to parallel-hand fringe ratios of the essentially unpolarized source 0Q 208, and is believed accurate to 0.5%. Other sources, such as AO 0235+164 and 0106+013, which are nearly unresolved in the unpolarized fringes, show clear signs of resolution in their polarized fringes. A preliminary map of the BL Lacertae object OJ 287 is compatible with a weakly-polarized optically-thick core and a highly-polarized optically-thin jet about 5 mas in length.