Nora I. Strom, Zachary F. Gerring, Marco Galimberti, Dongmei Yu, Matthew W. Halvorsen, Abdel Abdellaoui, Cristina Rodriguez-Fontenla, Julia M. Sealock, Tim Bigdeli, Jonathan R. Coleman, Behrang Mahjani, Jackson G. Thorp, Katharina Bey, Christie L. Burton, Jurjen J. Luykx, Gwyneth Zai, Silvia Alemany, Christine Andre, Kathleen D. Askland, Julia Bäckman, Nerisa Banaj, Cristina Barlassina, Judith Becker Nissen, O. Joseph Bienvenu, Donald Black, Michael H. Bloch, Sigrid Børte, Rosa Bosch, Michael Breen, Brian P. Brennan, Helena Brentani, Joseph D. Buxbaum, Jonas Bybjerg-Grauholm, Enda M. Byrne, Judit Cabana-Dominguez, Beatriz Camarena, Adrian Camarena, Carolina Cappi, Angel Carracedo, Miguel Casas, Maria Cristina Cavallini, Valentina Ciullo, Edwin H. Cook, Jesse Crosby, Bernadette A. Cullen, Elles J. De Schipper, Richard Delorme, Srdjan Djurovic, Jason A. Elias, Xavier Estivill, Martha J. Falkenstein, Bengt T. Fundin, Lauryn 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 G. Hounie, Donald Hucks, Christina Hultman, Magdalena Janecka, Eric Jenike, Elinor K. Karlsson, Kara Kelley, Julia Klawohn, Janice E. Krasnow, Kristi Krebs, Christoph Lange, Nuria Lanzagorta, Daniel Levey, Kerstin Lindblad-Toh, Fabio Macciardi, Brion Maher, Brittany Mathes, Evonne McArthur, Nathaniel McGregor, Nicole C. McLaughlin, Sandra Meier, Euripedes C. 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 Ramirez, Scott Rauch, Abraham Reichenberg, Mark A. Riddle, Stephan Ripke, Maria C. Rosário, Aline S. Sampaio, Miriam A. Schiele, Anne Heidi Skogholt, Laura G. Sloofman, Jan Smit, María Soler Artigas, Laurent F. Thomas, Eric Tifft, Homero Vallada, Nathanial van Kirk, Jeremy Veenstra-VanderWeele, Nienke N. Vulink, Christopher P. Walker, Ying Wang, Jens R. Wendland, Bendik S. Winsvold, Yin Yao, Hang Zhou, Arpana Agrawal, Pino Alonso, Götz Berberich, Kathleen K. Bucholz, Cynthia M. Bulik, Danielle Cath, Damiaan Denys, Valsamma Eapen, Howard Edenberg, Peter Falkai, Thomas V. Fernandez, Abby J. Fyer, J. M. Gaziano, Dan A. Geller, Hans J. Grabe, Benjamin D. Greenberg, Gregory L. Hanna, Ian B. Hickie, David M. Hougaard, Norbert Kathmann, James Kennedy, Dongbing Lai, Mikael Landén, Stéphanie Le Hellard, Marion Leboyer, Christine Lochner, James T. McCracken, Sarah E. Medland, Preben B. Mortensen, Benjamin M. Neale, Humberto Nicolini, Merete Nordentoft, Michele Pato, Carlos Pato, David L. Pauls, John Piacentini, Christopher Pittenger, Danielle Posthuma, Josep Antoni Ramos-Quiroga, Steven A. Rasmussen, Margaret A. 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 Werge, Ole A. Andreassen, Anders D. Børglum, Susanne Walitza, Kristian Hveem, Bjarne K. 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 D. Arnold, Dorothy E. Grice, James A. Knowles, Helga Ask, Karin J. Verweij, Lea K. Davis, Dirk J. Smit, James J. Crowley, Jeremiah M. Scharf, Murray B. Stein, Joel Gelernter, Carol A. Mathews, Eske M. Derks, Manuel Mattheisen
{"title":"Genome-wide analyses identify 30 loci associated with obsessive–compulsive disorder","authors":"Nora I. Strom, Zachary F. Gerring, Marco Galimberti, Dongmei Yu, Matthew W. Halvorsen, Abdel Abdellaoui, Cristina Rodriguez-Fontenla, Julia M. Sealock, Tim Bigdeli, Jonathan R. Coleman, Behrang Mahjani, Jackson G. Thorp, Katharina Bey, Christie L. Burton, Jurjen J. Luykx, Gwyneth Zai, Silvia Alemany, Christine Andre, Kathleen D. Askland, Julia Bäckman, Nerisa Banaj, Cristina Barlassina, Judith Becker Nissen, O. Joseph Bienvenu, Donald Black, Michael H. Bloch, Sigrid Børte, Rosa Bosch, Michael Breen, Brian P. Brennan, Helena Brentani, Joseph D. Buxbaum, Jonas Bybjerg-Grauholm, Enda M. Byrne, Judit Cabana-Dominguez, Beatriz Camarena, Adrian Camarena, Carolina Cappi, Angel Carracedo, Miguel Casas, Maria Cristina Cavallini, Valentina Ciullo, Edwin H. Cook, Jesse Crosby, Bernadette A. Cullen, Elles J. De Schipper, Richard Delorme, Srdjan Djurovic, Jason A. Elias, Xavier Estivill, Martha J. Falkenstein, Bengt T. Fundin, Lauryn 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 G. Hounie, Donald Hucks, Christina Hultman, Magdalena Janecka, Eric Jenike, Elinor K. Karlsson, Kara Kelley, Julia Klawohn, Janice E. Krasnow, Kristi Krebs, Christoph Lange, Nuria Lanzagorta, Daniel Levey, Kerstin Lindblad-Toh, Fabio Macciardi, Brion Maher, Brittany Mathes, Evonne McArthur, Nathaniel McGregor, Nicole C. McLaughlin, Sandra Meier, Euripedes C. 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 Ramirez, Scott Rauch, Abraham Reichenberg, Mark A. Riddle, Stephan Ripke, Maria C. Rosário, Aline S. Sampaio, Miriam A. Schiele, Anne Heidi Skogholt, Laura G. Sloofman, Jan Smit, María Soler Artigas, Laurent F. Thomas, Eric Tifft, Homero Vallada, Nathanial van Kirk, Jeremy Veenstra-VanderWeele, Nienke N. Vulink, Christopher P. Walker, Ying Wang, Jens R. Wendland, Bendik S. Winsvold, Yin Yao, Hang Zhou, Arpana Agrawal, Pino Alonso, Götz Berberich, Kathleen K. Bucholz, Cynthia M. Bulik, Danielle Cath, Damiaan Denys, Valsamma Eapen, Howard Edenberg, Peter Falkai, Thomas V. Fernandez, Abby J. Fyer, J. M. Gaziano, Dan A. Geller, Hans J. Grabe, Benjamin D. Greenberg, Gregory L. Hanna, Ian B. Hickie, David M. Hougaard, Norbert Kathmann, James Kennedy, Dongbing Lai, Mikael Landén, Stéphanie Le Hellard, Marion Leboyer, Christine Lochner, James T. McCracken, Sarah E. Medland, Preben B. Mortensen, Benjamin M. Neale, Humberto Nicolini, Merete Nordentoft, Michele Pato, Carlos Pato, David L. Pauls, John Piacentini, Christopher Pittenger, Danielle Posthuma, Josep Antoni Ramos-Quiroga, Steven A. Rasmussen, Margaret A. 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 Werge, Ole A. Andreassen, Anders D. Børglum, Susanne Walitza, Kristian Hveem, Bjarne K. 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 D. Arnold, Dorothy E. Grice, James A. Knowles, Helga Ask, Karin J. Verweij, Lea K. Davis, Dirk J. Smit, James J. Crowley, Jeremiah M. Scharf, Murray B. Stein, Joel Gelernter, Carol A. Mathews, Eske M. Derks, Manuel Mattheisen","doi":"10.1038/s41588-025-02189-z","DOIUrl":null,"url":null,"abstract":"<p>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 <i>WDR6</i>, <i>DALRD3</i> and <i>CTNND1</i> 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<sub>1</sub> and D<sub>2</sub> 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.</p>","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"7 1","pages":""},"PeriodicalIF":31.7000,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature genetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s41588-025-02189-z","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
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 D1 and D2 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.
期刊介绍：
Nature Genetics publishes the very highest quality research in genetics. It encompasses genetic and functional genomic studies on human and plant traits and on other model organisms. Current emphasis is on the genetic basis for common and complex diseases and on the functional mechanism, architecture and evolution of gene networks, studied by experimental perturbation.
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-Molecular analysis of simple and complex genetic traits
-Cancer genetics
-Agricultural genomics
-Developmental genetics
-Regulatory variation in gene expression
-Strategies and technologies for extracting function from genomic data
-Pharmacological genomics
-Genome evolution
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