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Record W3210960311 · doi:10.1101/2021.10.13.21261078

Genome-wide association study identifies new locus associated with OCD

2021· preprint· en· W3210960311 on OpenAlexaff
Nora I. Strom, Dongmei Yu, Zachary F. Gerring, 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, Kathleen D. Askland, Cristina Barlassina, Judith Becker Nissen, Laura Bellodi, O. Joseph Bienvenu, Donald W. Black, Michael H. Bloch, Julia Boberg, Rosa Bosch, Michael S. Breen, Brian P. Brennan, Helena Brentani, Joseph D. Buxbaum, Jonas Bybjerg‐Grauholm, Enda M. Byrne, Beatríz Camarena, Adrian Camarena, Carolina Cappi, Ángel Carracedo, Miguel Casas, Maria Cristina Cavallini, Valentina Ciullo, Edwin H. Cook, Vladimir Coric, Bernadette Cullen, Elles de Schipper, Bernie Devlin, Srdjan Djurovic, Jason A. Elias, Lauren Erdman, Xavier Estivil, Martha J. Falkenstein, Bengt T. Fundín, Maiken E. Gabrielsen, Fernando S. Goes, Marco A. Grados, Jakob Grove, Wei Guo, Jan Haavik, Kristen Hagen, Alexandra Havdahl, Ana Gabriela Hounie, Donald Hucks, Christina M. Hultman, Magdalena Janecka, Michael A. Jenike, Elinor K. Karlsson, Julia Klawohn, Lambertus Klei, Janice Krasnow, Kristi Krebs, Jason W. Krompinger, Nuria Lanzagorta, Fabìo Macciardi, Brion S. Maher, 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, Teemu Palviainen, Fabrizio Piras, Federica Piras, Ann E. Pulver, Raquel Rabionet, Alfredo Ramı́rez, Scott L. Rauch, Abraham Reichenberg, Jennifer Reichert, Mark A. Riddle, Stephan Ripke, Aline S. Sampaio, Miriam A. Schiele, Laura Sloofman, Jan Smit, Janet L. Sobell, María Soler Artigas, Laurent F. Thomas, Homero Vallada, Jeremy Veenstra‐VanderWeele, Nienke Vulink, Christopher Walker, Ying Wang, Jens R. Wendland, Bendik S. Winsvold, Yin Yao Shugart, Pino Alonso, Götz Berberich, Cynthia M. Bulik, Daniëlle C. Cath, Daniele Cusi, Richard Delorme, Damiaan Denys, Valsamma Eapen, Peter Falkai, Thomas Fernandez, Abby J. Fyer, Daniel Geller, Hans J. Grabe, Benjamin D. Greenberg, Gregory L. Hanna, Ian B. Hickie, David M. Hougaard, Norbert Kathmann, James L. Kennedy, Kung‐Yee Liang, 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, Nancy L. Pedersen, John Piacentini, Christopher Pittenger, Daniëlle Posthuma, Josep Antoni Ramos‐Quiroga, Steven A. Rasmussen, Kerry J. Ressler, 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, 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, Andres Metspalu, 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, Carol A. Mathews, Eske M. Derks, Jeremiah M. Scharf, Manuel Mattheisen

Bibliographic record

VenuemedRxiv · 2021
Typepreprint
Languageen
FieldPsychology
TopicObsessive-Compulsive Spectrum Disorders
Canadian institutionsUniversity of CalgaryHealth Sciences CentreSunnybrook Health Science CentreDalhousie UniversityUniversity of TorontoWaypoint Centre for Mental Health CareCentre for Addiction and Mental HealthUniversity of British ColumbiaHospital for Sick ChildrenStructural Genomics Consortium
Fundersnot available
KeywordsGenome-wide association studyGenetic architectureSingle-nucleotide polymorphismGenetic associationHeritabilitySNPLocus (genetics)GeneticsBulimia nervosaPsychiatryBiologyPsychologyPhenotypeEating disordersGeneGenotype

Abstract

fetched live from OpenAlex

Obsessive-compulsive disorder (OCD) is a heritable disorder, but no definitive, replicated OCD susceptibility loci have yet been identified by any genome-wide association study (GWAS). Here, we report results from a GWAS in the largest OCD case-control sample (N = 14,140 OCD cases and N = 562,117 controls) to date. We explored the genetic architecture of OCD, including its genetic relationships to other psychiatric and non-psychiatric phenotypes. In the GWAS analysis, we identified one SNP associated with OCD at a genome-wide significant level. Subsequent gene-based analyses identified additional two genes as potentially implicated in OCD pathogenesis. All SNPs combined explained 16% of the heritability of OCD. We show sub-stantial positive genetic correlations between OCD and a range of psychiatric disorders, including anxiety disorders, anorexia nervosa, and major depression. We thus for the first time provide evidence of a genome-wide locus implicated in OCD and strengthen previous literature suggesting a polygenic nature of this 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 score0.004
Threshold uncertainty score0.012

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 communication0.0010.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0040.000

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 head0.017
GPT teacher head0.286
Teacher spread0.268 · 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

Citations34
Published2021
Admission routes1
Has abstractyes

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