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Record W3087062906 · doi:10.1101/2020.09.17.20187054

Genome-wide association study of over 40,000 bipolar disorder cases provides new insights into the underlying biology

2020· preprint· en· W3087062906 on OpenAlex
Niamh Mullins, Andreas J. Forstner, Kevin S. O’Connell, Brandon J. Coombes, Jonathan R. I. Coleman, Zhen Qiao, Thomas D. Als, Tim B. Bigdeli, Sigrid Børte, Julien Bryois, Alexander W. Charney, Ole Kristian Drange, Michael J. Gandal, Saskia P. Hagenaars, Masashi Ikeda, Nolan Kamitaki, Minsoo Kim, Kristi Krebs, Georgia Panagiotaropoulou, Brian M. Schilder, Laura Sloofman, Stacy Steinberg, Vassily Trubetskoy, Bendik S. Winsvold, Hong‐Hee Won, Liliya Abramova, Kristina Adorjan, Esben Agerbo, Mariam Al Eissa, Diego Albani, Ney Alliey‐Rodriguez, Adebayo Anjorin, Verneri Antilla, Anastasia Antoniou, Swapnil Awasthi, Ji Hyun Baek, Marie Bækvad‐Hansen, Nicholas Bass, Michael Bauer, Eva C. Beins, Sarah E. Bergen, Armin Birner, Carsten Bøcker Pedersen, Erlend Bøen, Marco P. Boks, Rosa Bosch, Murielle Brum, Ben Brumpton, Nathalie Brunkhorst-Kanaan, Monika Budde, Jonas Bybjerg‐Grauholm, William Byerley, Murray J. Cairns, Miguel Casas, Pablo Cervantes, Toni‐Kim Clarke, Cristiana Cruceanu, Alfredo B. Cuéllar‐Barboza, Julie M. Cunningham, David Curtis, Piotr M. Czerski, Anders M. Dale, Nina Dalkner, Friederike S. David, Franziska Degenhardt, Srdjan Djurovic, Amanda Dobbyn, Athanasios Douzenis, Torbjørn Elvsåshagen, Valentina Escott‐Price, I. Nicol Ferrier, Alessia Fiorentino, Tatiana Foroud, Liz Forty, Josef Frank, Oleksandr Frei, Nelson B. Freimer, Louise Frisén, Katrin Gade, Julie Garnham, Joel Gelernter, Marianne Giørtz Pedersen, Ian R. Gizer, Scott D. Gordon, Katherine Gordon‐Smith, Tiffany A. Greenwood, Jakob Grove, José Guzmán‐Parra, Kyooseob Ha, Magnús Haraldsson, Martin Hautzinger, Urs Heilbronner, Dennis Hellgren, Stefan Herms, Per Hoffmann, Peter Holmans, Laura M. Huckins, Stéphane Jamain, Jessica Johnson, János Kálmán, James L. Kennedy, Sarah Kittel‐Schneider, James A. Knowles, Manolis Kogevinas, Maria Koromina, Thorsten M. Kranz, Henry R. Kranzler, Michiaki Kubo, Ralph Kupka, Steven A. Kushner, Catharina Lavebratt, Jacob Lawrence, Markus Leber, Heon‐Jeong Lee, Phil H. Lee, Shawn Levy, Cathryn M. Lewis, Calwing Liao, Susanne Lucae, Martin Lundberg, Donald J. MacIntyre, Sigurður H. Magnússon, Wolfgang Maier, Adam X. Maihofer, Dolores Malaspina, Eirini Maratou, Lina Martinsson, Manuel Mattheisen, Steven A. McCarroll, Nathaniel W. McGregor, Peter McGuffin, James McKay, Helena Medeiros, Sarah E. Medland, Vincent Millischer, Grant W. Montgomery, Jennifer L. Moran, Derek W. Morris, Thomas W. Mühleisen, Niamh L. O’Brien, Claire O’Donovan, Loes M. Olde Loohuis, Lilijana Oruč, Sergi Papiol, Antonio F. Pardiñas, Amy Perry, Andrea Pfennig, Evgenia Porichi, James B. Potash, Digby Quested, Towfique Raj, Mark Hyman Rapaport, J. Raymond DePaulo, Eline J. Regeer, John P. Rice, Fabio Rivas, Margarita Rivera, Julian Roth, Panos Roussos, Douglas M. Ruderfer, Cristina Sánchez‐Mora, Eva C. Schulte, Fanny Senner, Sally I. Sharp, Paul D. Shilling, Engilbert Sigurðsson, Lea Sirignano, Claire Slaney, Olav B. Smeland, Daniel J. Smıth, Janet L. Sobell, Christine Søholm Hansen, María Soler Artigas, Anne T. Spijker, Dan J. Stein, John S. Strauss, Beata Świątkowska, Chikashi Terao, Thorgeir E. Thorgeirsson, Claudio Toma, Paul A. Tooney, Evangelia Eirini Tsermpini, Marquis P. Vawter, Helmut Vedder, James Walters, Stephanie H. Witt, Simon Xi, Wei Xu, Jessica Yang, Allan H. Young, Hannah Young, Peter P. Zandi, Hang Zhou, Lea Zillich, HUNT All-In Psychiatry, Rolf Adolfsson, Ingrid Agartz, Martin Alda, Lars Alfredsson, Gulja Babadjanova, Lena Backlund, Bernhard T. Baune, Frank Bellivier, Susanne Bengesser, Wade H. Berrettini, Douglas Blackwood, Michael Boehnke, Anders D. Børglum, Gerome Breen, Vaughan J. Carr, Stanley V. Catts, Aiden Corvin, Nicholas Craddock, Udo Dannlowski, Dimitris Dikeos, Tõnu Esko, Bruno Étain, Panagiotis Ferentinos, Mark A. Frye, Janice M. Fullerton, Micha Gawlik, Elliot S. Gershon, Fernando S. Goes, Melissa J. Green, Maria Grigoroiu‐Serbânescu, Joanna Hauser, Frans A. Henskens, Jan Hillert, Kyung Sue Hong, David M. Hougaard, Christina M. Hultman, Kristian Hveem, Nakao Iwata, Assen Jablensky, Ian Jones, Lisa Jones, René S. Kahn, John R. Kelsoe, George Kirov, Mikael Landén, Marion Leboyer, Qingqin S. Li, Jolanta Lissowska, Christine Löchner, Carmel M. Loughland, Nicholas G. Martin, Carol A. Mathews, Fermín Mayoral, Susan L. McElroy, Andrew M. McIntosh, Francis J. McMahon, Ingrid Melle, Patricia T. Michie, Lili Milani, Philip B. Mitchell, Gunnar Morken, Ole Mors, Preben Bo Mortensen, Bryan Mowry, Bertram Müller-Myhsok, R Myers, Benjamin M. Neale, Caroline M. Nievergelt, Merete Nordentoft, Markus M. Nöthen, Michael O‘Donovan, Ketil J. Øedegaard, Tomas Olsson, Michael J. Owen, Sara A. Paciga, Christos Pantelis, Carlos N. Pato, Michele T. Pato, George P. Patrinos, Roy H. Perlis, Daniëlle Posthuma, Josep Antoni Ramos‐Quiroga, Andreas Reif, Eva Z. Reininghaus, Marta Ribasés, Marcella Rietschel, Stephan Ripke, Guy A. Rouleau, Takeo Saito, Ulrich Schall, Martin Schalling, Peter R. Schofield, Thomas G. Schulze, Laura J. Scott, Rodney J. Scott, Alessandro Serretti, Cynthia Shannon Weickert, Jordan W. Smoller, Hreinn Stefánsson, Eystein Stordal, Fabian Streit, Patrick F. Sullivan, Gustavo Turecki, Eduard Vieta, John B. Vincent, Irwin D. Waldman, Thomas W. Weickert, Thomas Werge, Naomi R. Wray, John‐Anker Zwart, Joanna M. Biernacka, John I. Nürnberger, Sven Cichon, Howard J. Edenberg, Eli A. Stahl, Andrew McQuillin, Arianna Di Florio, Roel A. Ophoff, Ole A. Andreassen

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenuemedRxiv · 2020
Typepreprint
Languageen
FieldMedicine
TopicBipolar Disorder and Treatment
Canadian institutionsPublic Health OntarioMcGill UniversityDalhousie UniversityMontreal Neurological Institute and HospitalUniversity of TorontoCentre for Addiction and Mental HealthMcGill University Health Centre
FundersNational Institute of Mental Health
KeywordsGenome-wide association studyBiologyBipolar disorderGeneGeneticsDruggabilityGenetic associationPrefrontal cortexExpression quantitative trait lociNeuroscienceSingle-nucleotide polymorphismGenotypeCognition

Abstract

fetched live from OpenAlex

Abstract Bipolar disorder (BD) is a heritable mental illness with complex etiology. We performed a genome-wide association study (GWAS) of 41,917 BD cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. BD risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating eQTL data implicated 15 genes robustly linked to BD via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of BD subtypes indicated high but imperfect genetic correlation between BD type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of BD, identify novel therapeutic leads and prioritize genes for functional follow-up studies.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.043
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.047
GPT teacher head0.311
Teacher spread0.264 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it