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Record W2743277997 · doi:10.1101/173062

Genome-wide association study identifies 30 Loci Associated with Bipolar Disorder

2017· preprint· en· W2743277997 on OpenAlexafffund
Eli A. Stahl, Gerome Breen, Andreas J. Forstner, Andrew McQuillin, Stephan Ripke, Vassily Trubetskoy, Manuel Mattheisen, Yunpeng Wang, Jonathan R. I. Coleman, Helena Gaspar, Christiaan de Leeuw, Stacy Steinberg, Jennifer M. Whitehead Pavlides, Maciej Trzaskowski, Tune H. Pers, Peter Holmans, Liam Abbott, Esben Agerbo, Huda Akil, Diego Albani, Ney Alliey‐Rodriguez, Thomas D. Als, Adebayo Anjorin, Verneri Antilla, Swapnil Awasthi, Judith A. Badner, Marie Bækvad‐Hansen, Jack D. Barchas, Nicholas Bass, Michael Bauer, Richard A. Belliveau, Sarah E. Bergen, Carsten Bøcker Pedersen, Erlend Bøen, Marco P. Boks, James Boocock, Monika Budde, William E. Bunney, Margit Burmeister, Jonas Bybjerg‐Grauholm, William Byerley, Miguel Casas, Felecia Cerrato, Pablo Cervantes, Kimberly Chambert, Alexander W. Charney, Danfeng Chen, Claire Churchhouse, Toni‐Kim Clarke, William Coryell, David W. Craig, Cristiana Cruceanu, David Curtis, Piotr M. Czerski, Anders M. Dale, Simone de Jong, Franziska Degenhardt, Jurgen Del‐Favero, J. Raymond DePaulo, Srdjan Djurovic, Amanda Dobbyn, Ashley Dumont, Torbjørn Elvsåshagen, Valentina Escott‐Price, Chun Chieh Fan, Sascha B. Fischer, Matthew Flickinger, Tatiana Foroud, Liz Forty, Josef Frank, Christine Fraser, Louise Frisén, Katrin Gade, Diane Gage, Julie Garnham, Claudia Giambartolomei, Marianne Giørtz Pedersen, Jaqueline Goldstein, Scott D. Gordon, Katherine Gordon‐Smith, Elaine Green, Melissa J. Green, Tiffany A. Greenwood, Jakob Grove, Weihua Guan, JoséGuzman Parra, Marian L. Hamshere, Martin Hautzinger, Urs Heilbronner, Stefan Herms, Maria Hipolito, Per Hoffmann, Dominic Holland, Laura M. Huckins, Stéphane Jamain, Jessica Johnson, Anders Juréus, Radhika Kandaswamy, Robert Karlsson, James L. Kennedy, Sarah Kittel‐Schneider, Sarah Knott, James A. Knowles, Manolis Kogevinas, Anna C. Koller, Ralph Kupka, Catharina Lavebratt, Jacob Lawrence, William Lawson, Markus Leber, Phil H. Lee, Shawn Levy, Jun Z. Li, Chunyu Liu, Susanne Lucae, Anna Maaser, Donald J. MacIntyre, Pamela B. Mahon, Wolfgang Maier, Lina Martinsson, Steve McCarroll, Peter McGuffin, Melvin G. McInnis, James McKay, Helena Medeiros, Sarah E. Medland, Fan Meng, Lili Milani, Grant W. Montgomery, Derek W. Morris, Thomas W. Mühleisen, Niamh Mullins, Hoang Nguyen, Caroline M. Nievergelt, Annelie Nordin Adolfsson, Evaristus Nwulia, Claire O’Donovan, Loes M. Olde Loohuis, Anil P. S. Ori, Lilijana Oruč, Urban Ösby, Roy H. Perlis, Amy Perry, Andrea Pfennig, James B. Potash, Shaun Purcell, Eline J. Regeer, Andreas Reif, Céline S. Reinbold, John P. Rice, Fabio Rivas, Margarita Rivera, Panos Roussos, Douglas M. Ruderfer, Euijung Ryu, Cristina Sánchez‐Mora, Alan F. Schatzberg, William A. Scheftner, Nicholas J. Schork, Cynthia Shannon Weickert, Tatyana Shehktman, Paul D. Shilling, Engilbert Sigurðsson, Claire Slaney, Olav B. Smeland, Janet L. Sobell, Christine Søholm Hansen, Anne T. Spijker, David St Clair, Michael Steffens, John S. Strauss, Fabian Streit, Jana Strohmaier, Szabolcs Szelinger, Robert C. Thompson, Thorgeir E. Thorgeirsson, Jens Treutlein, Helmut Vedder, Weiqing Wang, Stanley J. Watson, Thomas W. Weickert, Stephanie H. Witt, Simon Xi, Wei Xu, Allan H. Young, Peter P. Zandi, Peng Zhang, Sebastian Zöllner, Rolf Adolfsson, Ingrid Agartz, Martin Alda, Lena Backlund, Bernhard T. Baune, Frank Bellivier, Wade H. Berrettini, Joanna M. Biernacka, Douglas Blackwood, Michael Boehnke, Anders D. Børglum, Aiden Corvin, Nicholas Craddock, Mark J. Daly, Udo Dannlowski, Tõnu Esko, Bruno Étain, Mark A. Frye, Janice M. Fullerton, Elliot S. Gershon, Michael Gill, Fernando S. Goes, Maria Grigoroiu‐Serbânescu, Joanna Hauser, David M. Hougaard, Christina M. Hultman, Ian Jones, Lisa Jones, RenéS Kahn, George Kirov, Mikael Landén, Marion Leboyer, Cathryn M. Lewis, Qingqin S. Li, Jolanta Lissowska, Nicholas G. Martin, Fermín Mayoral, Susan L. McElroy, Andrew M. McIntosh, Francis J. McMahon, Ingrid Melle, Andres Metspalu, Philip B. Mitchell, Gunnar Morken, Ole Mors, Preben Bo Mortensen, Bertram Müller-Myhsok, R Myers, Benjamin M. Neale, Vishwajit L. Nimgaonkar, Merete Nordentoft, Markus M. Nöthen, Michael O‘Donovan, Ketil J. Øedegaard, Michael J. Owen, Sara A. Paciga, Carlos N. Pato, Michele T. Pato, Daniëlle Posthuma, Josep Antoni Ramos‐Quiroga, Marta Ribasés, Marcella Rietschel, Guy A. Rouleau, Martin Schalling, Peter R. Schofield, Thomas G. Schulze, Alessandro Serretti, Jordan W. Smoller, Hreinn Stefánsson, Eystein Stordal, Patrick F. Sullivan, Gustavo Turecki, Eduard Vieta, John B. Vincent, Thomas Werge, John I. Nürnberger, Naomi R. Wray, Arianna Di Florio, Howard J. Edenberg, Sven Cichon, Roel A. Ophoff, Laura J. Scott, Ole A. Andreassen, John R. Kelsoe, Pamela Sklar

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2017
Typepreprint
Languageen
FieldMedicine
TopicBipolar Disorder and Treatment
Canadian institutionsUniversity of TorontoAmgen (Canada)
FundersNational Institute of Mental HealthMedical Research CouncilNational Institutes of HealthVictoria General Hospital FoundationCentro de Investigación Biomédica en Red de Salud MentalUniversità di BolognaEuropean CommissionCanadian Institutes of Health ResearchNational Institute for Health and Care ResearchNational Alliance for Research on Schizophrenia and DepressionMichael Smith Health Research BCUniversitat de BarcelonaWellcome Trust
KeywordsBipolar disorderManiaGenome-wide association studySchizophrenia (object-oriented programming)Major depressive disorderGenetic associationGeneticsPsychiatryMedicinePsychologyBiologyGeneSingle-nucleotide polymorphismGenotypeLithium (medication)Mood

Abstract

fetched live from OpenAlex

ABSTRACT Bipolar disorder is a highly heritable psychiatric disorder that features episodes of mania and depression. We performed the largest genome-wide association study to date, including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 sentinel variants at loci with P<1×10 -4 in an independent sample of 9,412 cases and 137,760 controls. In the combined analysis, 30 loci reached genome-wide significant evidence for association, of which 20 were novel. These significant loci contain genes encoding ion channels and neurotransmitter transporters ( CACNA1C , GRIN2A , SCN2A , SLC4A1 ), synaptic components ( RIMS1 , ANK3 ), immune and energy metabolism components. Bipolar disorder type I (depressive and manic episodes; ~ 73% of our cases) is strongly genetically correlated with schizophrenia whereas bipolar disorder type II (depressive and hypomanic episodes; ~ 17% of our cases) is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential new biological mechanisms for bipolar disorder.

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.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.014
GPT teacher head0.236
Teacher spread0.223 · 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

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations255
Published2017
Admission routes2
Has abstractyes

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Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicBipolar Disorder and TreatmentFrench-language works237,207