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

作者：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 Justin Luykx, Gwyneth C. Zai, Silvia Alemany, Christine André, Kathleen D. Askland, Julia Bäckman, Nerisa Banaj, Cristina Barlassina, Judith Becker Nissen, Oscar 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 J. de Schipper, Richard Delorme, Srdjan Djurovic, Jason A. Elias, Xavier Estivill, Martha J. Falkenstein, Bengt T. Fundín, Lauryn E. Garner, Christina M. Gironda, Fernando S. Goes, Marco A. Grados, Jakob Grove, Wei Guo, Jan Haavik, Kristen Hagen, Kelly M. Harrington, Alexandra Havdahl, Kira Daniela Höffler, Ana Gabriela Hounie, Donald Hucks, Christina M. Hultman, Magdalena Janecka, Eric A. Jenike, Elinor K. Karlsson, Kara N. Kelley, Julia Klawohn, Janice E. Krasnow, Kristi Krebs, Christoph Lange, Nuria Lanzagorta, Daniel F. Levey, Kerstin Lindblad‐Toh, Fabio M. Macciardi, Brion S. Maher, Brittany M. Mathes, Evonne McArthur, Nathaniel W. McGregor, Nicole C R McLaughlin, Sandra Melanie Meier, Eurı́pedes Constantino Miguel, Maureen Mulhern, Paul Sasha Nestadt, Erika L. Nurmi, Kevin Sean 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 Conceição do Rosário, Aline S. Sampaio, Miriam A. Schiele, Anne Heidi Skogholt, Laura Gail Sloofman, Jan H Smit, María Soler Artigas, Laurent F. Thomas, Eric D. Tifft, Homero Vallada, Nathaniel P. Van Kirk, Jeremy M. Veenstra-VanderWeele, Nienke C C Vulink, Christopher Walker, Ying Wang, Jens R. Wendland, Bendik Slagsvold Winsvold, Yin Yao, Hang Zhou, Estonian Biobank, Andres Metspalu, Tõnu Esko, Reedik Mägi, Mari Nelis, Georgi Hudjashov, Chris German, Arpana Agrawal, Pino Alonso, Götz Berberich, Kathleen Keenan Bucholz, Cynthia Marie Bulik, Daniëlle C. Cath, Damiaan A J P Denys, Valsamma Eapen, Howard J. Edenberg, Peter Falkai, Thomas V. Fernandez, Abby J. Fyer, J. Michael Gaziano, DANIEL A. GELLER, Hans Jörgen Grabe, Benjamin D. Greenberg, Gregory L. Hanna, Ian Bernard Hickie, DAVID MICHAEL HOUGAARD, Norbert Kathmann, James L. Kennedy, Dongbing Lai, Mikael Landén, Stéphanie Le Hellard, Marion Leboyer, Christine Löchner, James T. McCracken, Sarah Elizabeth Medland, Preben Bo Mortensen, Benjamin M. Neale, Humberto Nicolini, Merete Nordentoft, Michele T. Pato, Carlos N. Pato, David L. Pauls, John C. Piacentini, Christopher Pittenger, Daniëlle Posthuma, Josep Antoni Ramos‐Quiroga, Steven A. Rasmussen, Margaret Anne Richter, David R. Rosenberg, Stephan Ruhrmann, JACK F. SAMUELS, Sven Sandin, Paul Sandor, Gianfranco Spalletta, Dan J. Stein, S. Evelyn Stewart, Eric A. Storch, Barbara E. Stranger, Maurizio Turiel, Thomas Mears Werge, Ole A. Andreassen, Anders Dupont Børglum, Susanne Walitza, Kristian Hveem, Bjarne K. A. Hansen, Christian Rück, Nicholas G. Martin, Lili A. Milani, Ole N Mors, Ted Reichborn‐Kjennerud, Marta Ribasés, Gerd Kvale, David Mataix‐Cols, Katharina Domschke, Edna Grünblatt, Michael Wagner, John‐Anker Zwart, Gerome D. Breen, Gerald Nestadt, Jaakko A. Kaprio, Paul Daniel Arnold, Dorothy E. Grice, James A. Knowles, Helga Ask, Karin J. H. Verweij, Lea Karatheodoris Davis, Dirk J. A. Smit, James J. Crowley, Jeremiah M. Scharf, Murray B. Stein, Joel E. Gelernter, Carol A. Mathews, Eske M. Derks, Manuel Mattheisen · 发表于：Nature Genetics · 年份：2025 · DOI：10.1038/s41588-025-02189-z · 被引用次数：61 · 研究领域：Obsessive-Compulsive Spectrum Disorders、Autism Spectrum Disorder Research

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 and CTNND1 and multiple genes in the major histocompatibility complex (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 the cortex, along with D 1 and D 2 type dopamine receptor-containing medium spiny neurons. OCD genetic risk was shared with 65 of 112 additional phenotypes, including all 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.