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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
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- 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.
Polygenic contributions to alcohol use and alcohol use disorders across population-based and clinically ascertained samples
- Emma C. Johnson, Sandra Sanchez-Roige, Laura Acion, Mark J. Adams, Kathleen K. Bucholz, Grace Chan, Michael J. Chao, David B. Chorlian, Danielle M. Dick, Howard J. Edenberg, Tatiana Foroud, Caroline Hayward, Jon Heron, Victor Hesselbrock, Matthew Hickman, Kenneth S. Kendler, Sivan Kinreich, John Kramer, Sally I-Chun Kuo, Samuel Kuperman, Dongbing Lai, Andrew M. McIntosh, Jacquelyn L. Meyers, Martin H. Plawecki, Bernice Porjesz, David Porteous, Marc A. Schuckit, Jinni Su, Yong Zang, Abraham A. Palmer, Arpana Agrawal, Toni-Kim Clarke, Alexis C. Edwards
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- Journal:
- Psychological Medicine / Volume 51 / Issue 7 / May 2021
- Published online by Cambridge University Press:
- 20 January 2020, pp. 1147-1156
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Background
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
MethodsWe examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
ResultsIn COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
ConclusionsAUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
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- By Mitchell Aboulafia, Frederick Adams, Marilyn McCord Adams, Robert M. Adams, Laird Addis, James W. Allard, David Allison, William P. Alston, Karl Ameriks, C. Anthony Anderson, David Leech Anderson, Lanier Anderson, Roger Ariew, David Armstrong, Denis G. Arnold, E. J. Ashworth, Margaret Atherton, Robin Attfield, Bruce Aune, Edward Wilson Averill, Jody Azzouni, Kent Bach, Andrew Bailey, Lynne Rudder Baker, Thomas R. Baldwin, Jon Barwise, George Bealer, William Bechtel, Lawrence C. Becker, Mark A. Bedau, Ernst Behler, José A. Benardete, Ermanno Bencivenga, Jan Berg, Michael Bergmann, Robert L. Bernasconi, Sven Bernecker, Bernard Berofsky, Rod Bertolet, Charles J. Beyer, Christian Beyer, Joseph Bien, Joseph Bien, Peg Birmingham, Ivan Boh, James Bohman, Daniel Bonevac, Laurence BonJour, William J. Bouwsma, Raymond D. Bradley, Myles Brand, Richard B. Brandt, Michael E. Bratman, Stephen E. Braude, Daniel Breazeale, Angela Breitenbach, Jason Bridges, David O. Brink, Gordon G. 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- By Graham Allan, Donna M. Allen, Irwin Altman, Arthur Aron, Donald H. Baucom, Steven R. H. Beach, Ellen Berscheid, Rosemary Blieszner, Jeffrey Boase, Tyfany M. J. Boettcher, Barbara B. Brown, Abraham P. Buunk, Lorne Campbell, Daniel J. Canary, Rodney Cate, John P. Caughlin, Mahnaz Charania, Jennie Y. Chen, F. Scott Christopher, Jennifer A. Clarke, Marilyn Coleman, W. Andrew Collins, Michael K. Coolsen, Nathan R. Cottle, Carolyn E. Cutrona, Marianne Dainton, Valerian J. Derlega, Lisa M. Diamond, Pieternel Dijkstra, Steve Duck, Pearl A. Dykstra, Norman B. Epstein, Beverley Fehr, Frank D. Fincham, Helen E. Fisher, Julie Fitness, Garth J. O. Fletcher, Myron D. Friesen, Lawrence Ganong, Kelli A. Gardner, Jenny de Jong Gierveld, Robin Goodwin, Christine R. Gray, Kathryn Greene, David W. Harris, Willard W. Hartup, John H. Harvey, Kathi L. Heffner, Ted L. Huston, William J. Ickes, Emily A. Impett, Michael P. Johnson, Deborah J. Jones, Deborah A. Kashy, Janice K. Kiecolt‐Glaser, Jeffrey L. Kirchner, Brighid M. Kleinman, Galena H. Kline, Mark L. Knapp, Ascan Koerner, Jean‐Philippe Laurenceau, Kim Leon, Timothy J. Loving, Stephanie D. Madsen, Howard J. Markman, Alicia Mathews, Mario Mikulincer, Patricia Noller, Nickola C. Overall, Letitia Anne Peplau, Daniel Perlman, Sally Planalp, Urmila Pillay, Nicole D. Pleasant, Caryl E. Rusbult, Barbara R. Sarason, Irwin G. Sarason, Phillip R. Shaver, Alan L. Sillars, Jeffry A. Simpson, Susan Sprecher, Susan Stanton, Greg Strong, Catherine A. Surra, Anita L. Vangelisti, C. Arthur VanLear, Theo van Tilburg, Barry Wellman, Amy Wenzel, Carol M. Werner, Adam R. West, Sarah W. Whitton, Heike A. Winterheld
- Edited by Anita L. Vangelisti, University of Texas, Austin, Daniel Perlman, University of British Columbia, Vancouver
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- Book:
- The Cambridge Handbook of Personal Relationships
- Published online:
- 05 June 2012
- Print publication:
- 05 June 2006, pp xvii-xxii
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Historical Studies of the English Parliament. Edited by E. B. Fryde and Edward Miller. (Cambridge: Cambridge University Press, 1970. 2 vols. [Vol. 1, Origins to 1399; Pp. 387; Vol. 2, 1399 to 1603; Pp. 350.] $11.00 each vol. Also available in paperback.)
- John Clarke Adams
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- Journal:
- American Political Science Review / Volume 65 / Issue 4 / December 1971
- Published online by Cambridge University Press:
- 01 August 2014, p. 1208
- Print publication:
- December 1971
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Europe Ascendant: The International Politics of Unification. By George Liska. (Baltimore: The Johns Hopkins Press. 1964. Pp. 182. $4.50.)
- John Clarke Adams
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- Journal:
- American Political Science Review / Volume 58 / Issue 4 / December 1964
- Published online by Cambridge University Press:
- 01 August 2014, p. 1052
- Print publication:
- December 1964
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The Implementation of the Italian Constitution
- John Clarke Adams, Paolo Barile
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- Journal:
- American Political Science Review / Volume 47 / Issue 1 / March 1953
- Published online by Cambridge University Press:
- 02 September 2013, pp. 61-83
- Print publication:
- March 1953
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The new Italian Constitution was written by the 556 deputies the Italian people elected to their first Constitutional Assembly on June 2, 1946. The Assembly approved the Constitution on December 22, 1947, by a vote of 453 favorable, 62 opposed, and 31 absent. After this approval the Constitution was promulgated by the Provisional President of Italy, Enrico de Nicola, and became effective ten days later, on January 1, 1948. Numerous evaluations of the Constitution are available, and it is not our purpose here to duplicate this work. We are concerned solely with discovering to what extent the Constitution was actually in effect during the four and one-half year period following its promulgation and with explaining, if possible, why there has been so much delay in implementing some of its basic provisions.
What we shall find is that some enabling legislation was passed by the Constitutional Assembly in the interim period between the effective date of the Constitution and the election of the first Parliament in April, 1948. Parliament has implemented a few more constitutional provisions, but vast and basic sections of the Constitution are still ineffective, owing to Parliament's inaction. To a lesser degree the administration and the courts are in a position to implement the Constitution.