MétaCan
Menu
Back to cohort
Record W4392968969 · doi:10.1101/2024.03.13.24304161

Genome-wide analyses identify 30 loci associated with obsessive-compulsive disorder

2024· preprint· en· W4392968969 on OpenAlexafffund
Nora I. Strom, Zachary F. Gerring, Marco Galimberti, Dongmei Yu, Matthew Halvorsen, Abdel Abdellaoui, Cristina Rodriguez‐Fontenla, Julia Sealock, Tim B. Bigdeli, Jonathan R. I. Coleman, Behrang Mahjani, Jackson G. Thorp, Katharina Bey, Christie L. Burton, Jurjen J. Luykx, Gwyneth Zai, Silvia Alemany, Christine André, Kathleen D. Askland, Nerisa Banaj, Cristina Barlassina, Judith Becker Nissen, O. Joseph Bienvenu, Donald W. Black, Michael H. Bloch, Sigrid Børte, Rosa Bosch, Michael S. Breen, Brian P. Brennan, Helena Brentani, Joseph D. Buxbaum, Jonas Bybjerg‐Grauholm, Enda M. Byrne, Judit Cabana‐Domínguez, Beatríz Camarena, Adrian Camarena, Carolina Cappi, Ángel Carracedo, Miguel Casas, Maria Cristina Cavallini, Valentina Ciullo, Edwin H. Cook, Jesse M. Crosby, Bernadette Cullen, Elles de Schipper, Richard Delorme, Srdjan Djurovic, Jason A. Elias, Xavier Estivill, Martha J. Falkenstein, Bengt T. Fundín, Lauryn E. Garner, Christina Gironda, Fernando S. Goes, Marco A. Grados, Jakob Grove, Wei Guo, Jan Haavik, Kristen Hagen, Kelly Harrington, Alexandra Havdahl, Kira D. Höffler, Ana Gabriela Hounie, Donald Hucks, Christina M. Hultman, Magdalena Janecka, Eric Jenike, Elinor K. Karlsson, Kara N. Kelley, Julia Klawohn, Janice Krasnow, Kristi Krebs, Christoph Lange, Nuria Lanzagorta, Daniel F. Levey, Kerstin Lindblad‐Toh, Fabìo Macciardi, Brion S. Maher, Brittany M. Mathes, Evonne McArthur, Nathaniel W. McGregor, Nicole McLaughlin, Sandra Meier, Eurı́pedes Constantino Miguel, Maureen Mulhern, Paul S. Nestadt, Erika L. Nurmi, Kevin S. O’Connell, Lisa Osiecki, Olga Therese Ousdal, Teemu Palviainen, Nancy L. Pedersen, Fabrizio Piras, Federica Piras, Sriramya Potluri, Raquel Rabionet, Alfredo Ramı́rez, Scott L. Rauch, Abraham Reichenberg, Mark A. Riddle, Stephan Ripke, Maria C. Rosário, Aline S. Sampaio, Miriam A. Schiele, Anne Heidi Skogholt, Laura Sloofman, Jan Smit, María Soler Artigas, Laurent F. Thomas, Eric D. Tifft, Homero Vallada, Nathanial van Kirk, Jeremy Veenstra‐VanderWeele, Nienke Vulink, Christopher Walker, Ying Wang, Jens R. Wendland, Bendik S. Winsvold, Yin Yao Shugart, Hang Zhou, Arpana Agrawal, Pino Alonso, Götz Berberich, Kathleen K. Bucholz, Cynthia M. Bulik, Daniëlle C. Cath, Damiaan Denys, Valsamma Eapen, Howard J. Edenberg, Peter Falkai, Thomas Fernandez, Abby J. Fyer, J. Michael Gaziano, Dan Geller, Hans J. Grabe, Benjamin D. Greenberg, Gregory L. Hanna, Ian B. Hickie, David M. Hougaard, Norbert Kathmann, James L. Kennedy, Dongbing Lai, Mikael Landén, Stéphanie Le Hellard, Marion Leboyer, Christine Löchner, James T. McCracken, Sarah E. Medland, Preben Bo Mortensen, Benjamin M. Neale, Humberto Nicolini, Merete Nordentoft, Michele T. Pato, Carlos N. Pato, David L. Pauls, John Piacentini, Christopher Pittenger, Daniëlle Posthuma, Josep Antoni Ramos‐Quiroga, Steven A. Rasmussen, Margaret A. Richter, David R. Rosenberg, Stephan Ruhrmann, Jack Samuels, Sven Sandin, Paul Sandor, Gianfranco Spalletta, Dan J. Stein, S. Evelyn Stewart, Eric A. Storch, Barbara E. Stranger, Maurizio Turiel, Thomas Werge, Ole A. Andreassen, Anders D. Børglum, Susanne Walitza, Kristian Hveem, Bjarne Hansen, Christian Rück, Nicholas G. Martin, Lili Milani, Ole Mors, Ted Reichborn‐Kjennerud, Marta Ribasés, Gerd Kvale, David Mataix‐Cols, Katharina Domschke, Edna Grünblatt, Michael Wagner, John‐Anker Zwart, Gerome Breen, Gerald Nestadt, Jaakko Kaprio, Paul Arnold, Dorothy E. Grice, James A. Knowles, Helga Ask, Karin J. H. Verweij, Lea K. Davis, Dirk J. A. Smit, James J. Crowley, Jeremiah M. Scharf, Murray B. Stein, Joel Gelernter, Carol A. Mathews, Eske M. Derks, Manuel Mattheisen

Bibliographic record

VenuemedRxiv · 2024
Typepreprint
Languageen
FieldPsychology
TopicObsessive-Compulsive Spectrum Disorders
Canadian institutionsUniversity of CalgaryBC Mental Health & Substance Use ServicesHealth Sciences CentreSunnybrook Health Science CentreMcMaster UniversityBC Children's HospitalDalhousie UniversityUniversity of TorontoCentre for Addiction and Mental HealthUniversity of British ColumbiaHospital for Sick Children
FundersNational Center for Advancing Translational SciencesNational Center for Research ResourcesNational Institute of Mental HealthFaculty of Medicine and Health, University of SydneyInstituto de Salud Carlos IIINational Health and Medical Research CouncilNIHR Maudsley Biomedical Research CentreMindich Child Health and Development Institute, Icahn School of Medicine at Mount SinaiCereal Partners WorldwideDepartment of Psychiatry, University of TorontoStanley Center for Psychiatric Research, Broad InstituteSUNY Downstate Medical CenterUniversity of North Carolina at Chapel HillNational Institutes of HealthNational Institute on AgingFundació Institut de Recerca Hospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaEuropean College of NeuropsychopharmacologyCentro de Investigación Biomédica en Red de Salud MentalNorwegian Institute of Public HealthHumboldt-Universität zu BerlinCampbell Family Mental Health Research InstituteHelse Midt-NorgeNovo NordiskBundesministerium für Bildung und ForschungUniversiteit van AmsterdamEuropean CommissionEuropean Regional Development FundKing's College LondonDepartment of Health and Social CareOntario Council on Graduate Studies, Council of Ontario UniversitiesMinistero dell’Istruzione, dell’Università e della RicercaNorges ForskningsrådQIMR Berghofer Medical Research InstituteAmsterdam University Medical CentersUniversidade de Santiago de CompostelaHelse- og OmsorgsdepartementetNational Center for PTSD, U.S. Department of Veterans AffairsDeutsche ForschungsgemeinschaftNorges Teknisk-Naturvitenskapelige UniversitetStichting Volksbond RotterdamNIH Clinical CenterTrond Mohn stiftelseFundación Instituto de Investigación Sanitaria de Santiago de CompostelaMcMaster UniversityMinisterio de Ciencia, Innovación y UniversidadesVetenskapsrådetRoy J. and Lucille A. Carver College of Medicine, University of IowaInstituto de Investigación Sanitaria de Santiago de CompostelaGeorgia Clinical and Translational Science AllianceStockholms Läns LandstingAarhus UniversitetVanderbilt University Medical CenterAarhus UniversitetshospitalBeatrice and Samuel A. Seaver FoundationMedical Research CouncilTartu ÜlikoolFundació la Marató de TV3Johns Hopkins UniversityFP7 HealthUniversity of TorontoOffice of Research and DevelopmentKarolinska InstitutetYale UniversityU.S. Department of Veterans AffairsAgència de Gestió d'Ajuts Universitaris i de RecercaNational Institute for Health and Care ResearchLundbeckfondenCenter for Innovative MedicineState University of New YorkH. Lundbeck A/SHospital for Sick ChildrenForskningsrådet om Hälsa, Arbetsliv och VälfärdBroad InstituteAFA FörsäkringMcLean HospitalVanderbilt UniversityMinistero della SaluteInternational OCD FoundationMassachusetts General Hospital
KeywordsGenome-wide association studyAssociation (psychology)Obsessive compulsiveGeneticsBiologyPsychologyPsychiatrySingle-nucleotide polymorphismGenotypeGenePsychotherapist

Abstract

fetched live from OpenAlex

Abstract Obsessive-compulsive disorder (OCD) affects ∼1% of children and adults and is partly caused by genetic factors. We conducted a genome-wide association study (GWAS) meta-analysis combining 53,660 OCD cases and 2,044,417 controls and identified 30 independent genome-wide significant loci. Gene-based approaches identified 249 potential effector genes for OCD, with 25 of these classified as the most likely causal candidates, including WDR6, DALRD3, CTNND1 and multiple genes in the MHC region. We estimated that ∼11,500 genetic variants explained 90% of OCD genetic heritability. OCD genetic risk was associated with excitatory neurons in the hippocampus and cortex, along with D1- and D2-type dopamine receptor-containing medium spiny neurons. OCD genetic risk was shared with 65 of 112 additional phenotypes, including all of the psychiatric disorders we examined. In particular, OCD shared genetic risk with anxiety, depression, anorexia nervosa, and Tourette syndrome, and was negatively associated with inflammatory bowel diseases, educational attainment, and body mass index.

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)0.001
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 score0.005
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.000

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 head0.032
GPT teacher head0.344
Teacher spread0.313 · 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

Citations25
Published2024
Admission routes2
Has abstractyes

Explore more

Same venuemedRxivSame topicObsessive-Compulsive Spectrum DisordersFrench-language works237,207