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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.
Looking Backward, Looking Forward: MLA Members Speak
- April Alliston, Elizabeth Ammons, Jean Arnold, Nina Baym, Sandra L. Beckett, Peter G. Beidler, Roger A. Berger, Sandra Bermann, J.J. Wilson, Troy Boone, Alison Booth, Wayne C. Booth, James Phelan, Marie Borroff, Ihab Hassan, Ulrich Weisstein, Zack Bowen, Jill Campbell, Dan Campion, Jay Caplan, Maurice Charney, Beverly Lyon Clark, Robert A. Colby, Thomas C. Coleman III, Nicole Cooley, Richard Dellamora, Morris Dickstein, Terrell Dixon, Emory Elliott, Caryl Emerson, Ann W. Engar, Lars Engle, Kai Hammermeister, N. N. Feltes, Mary Anne Ferguson, Annie Finch, Shelley Fisher Fishkin, Jerry Aline Flieger, Norman Friedman, Rosemarie Garland-Thomson, Sandra M. Gilbert, Laurie Grobman, George Guida, Liselotte Gumpel, R. K. Gupta, Florence Howe, Cathy L. Jrade, Richard A. Kaye, Calhoun Winton, Murray Krieger, Robert Langbaum, Richard A. Lanham, Marilee Lindemann, Paul Michael Lützeler, Thomas J. Lynn, Juliet Flower MacCannell, Michelle A. Massé, Irving Massey, Georges May, Christian W. Hallstein, Gita May, Lucy McDiarmid, Ellen Messer-Davidow, Koritha Mitchell, Robin Smiles, Kenyatta Albeny, George Monteiro, Joel Myerson, Alan Nadel, Ashton Nichols, Jeffrey Nishimura, Neal Oxenhandler, David Palumbo-Liu, Vincent P. Pecora, David Porter, Nancy Potter, Ronald C. Rosbottom, Elias L. Rivers, Gerhard F. Strasser, J. L. Styan, Marianna De Marco Torgovnick, Gary Totten, David van Leer, Asha Varadharajan, Orrin N. C. Wang, Sharon Willis, Louise E. Wright, Donald A. Yates, Takayuki Yokota-Murakami, Richard E. Zeikowitz, Angelika Bammer, Dale Bauer, Karl Beckson, Betsy A. Bowen, Stacey Donohue, Sheila Emerson, Gwendolyn Audrey Foster, Jay L. Halio, Karl Kroeber, Terence Hawkes, William B. Hunter, Mary Jambus, Willard F. King, Nancy K. Miller, Jody Norton, Ann Pellegrini, S. P. Rosenbaum, Lorie Roth, Robert Scholes, Joanne Shattock, Rosemary T. VanArsdel, Alfred Bendixen, Alarma Kathleen Brown, Michael J. Kiskis, Debra A. Castillo, Rey Chow, John F. Crossen, Robert F. Fleissner, Regenia Gagnier, Nicholas Howe, M. Thomas Inge, Frank Mehring, Hyungji Park, Jahan Ramazani, Kenneth M. Roemer, Deborah D. Rogers, A. LaVonne Brown Ruoff, Regina M. Schwartz, John T. Shawcross, Brenda R. Silver, Andrew von Hendy, Virginia Wright Wexman, Britta Zangen, A. Owen Aldridge, Paula R. Backscheider, Roland Bartel, E. M. Forster, Milton Birnbaum, Jonathan Bishop, Crystal Downing, Frank H. Ellis, Roberto Forns-Broggi, James R. Giles, Mary E. Giles, Susan Blair Green, Madelyn Gutwirth, Constance B. Hieatt, Titi Adepitan, Edgar C. Knowlton, Jr., Emanuel Mussman, Sally Todd Nelson, Robert O. Preyer, David Diego Rodriguez, Guy Stern, James Thorpe, Robert J. Wilson, Rebecca S. Beal, Joyce Simutis, Betsy Bowden, Sara Cooper, Wheeler Winston Dixon, Tarek el Ariss, Richard Jewell, John W. Kronik, Wendy Martin, Stuart Y. McDougal, Hugo Méndez-Ramírez, Ivy Schweitzer, Armand E. Singer, G. Thomas Tanselle, Tom Bishop, Mary Ann Caws, Marcel Gutwirth, Christophe Ippolito, Lawrence D. Kritzman, James Longenbach, Tim McCracken, Wolfe S. Molitor, Diane Quantic, Gregory Rabassa, Ellen M. Tsagaris, Anthony C. Yu, Betty Jean Craige, Wendell V. Harris, J. Hillis Miller, Jesse G. Swan, Helene Zimmer-Loew, Peter Berek, James Chandler, Hanna K. Charney, Philip Cohen, Judith Fetterley, Herbert Lindenberger, Julia Reinhard Lupton, Maximillian E. Novak, Richard Ohmann, Marjorie Perloff, Mark Reynolds, James Sledd, Harriet Turner, Marie Umeh, Flavia Aloya, Regina Barreca, Konrad Bieber, Ellis Hanson, William J. Hyde, Holly A. Laird, David Leverenz, Allen Michie, J. Wesley Miller, Marvin Rosenberg, Daniel R. Schwarz, Elizabeth Welt Trahan, Jean Fagan Yellin
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- Journal:
- PMLA / Publications of the Modern Language Association of America / Volume 115 / Issue 7 / December 2000
- Published online by Cambridge University Press:
- 23 October 2020, pp. 1986-2078
- Print publication:
- December 2000
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Evolution of Aspergillus niger and A. nidulans in glucose-limited chemostat cultures, as indicated by oscillations in the frequency of cycloheximide resistant and morphological mutants
- Richard J. SWIFT, Sally H. CRAIG, Marilyn G. Wiebe, Geoffrey D. ROBSON, Anthony P. J. TRINCI
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- Journal:
- Mycological Research / Volume 104 / Issue 3 / March 2000
- Published online by Cambridge University Press:
- 01 March 2000, pp. 333-337
- Print publication:
- March 2000
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Aspergillus niger and A. nidulans were grown separately in glucose-limited chemostat cultures on modified Vogel's medium. Periodic selection (the appearance of new mutant populations) in A. niger was determined by monitoring oscillations in the concentration of cycloheximide-resistant mycelial fragments in samples from the fermenter vessel. Using these data, the interval between the periodic selection of each new mutant population was 32±6 generations (mean±S.E.M.). Periodic selection in cycloheximide resistance in three morphologically distinct sub-populations of the A. niger culture averaged 36±2, 31±11 and 28±5 generations and these values were not significantly different from that of the whole population (32±6 generations). Also, it was possible to estimate the rate of evolution taking place in these cultures by monitoring oscillations in the frequency of morphological mutants. The intervals between the periodic selection of morphological mutant populations in A. niger and A. nidulans were 28±3 and 22±2 generations respectively.