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Genome-wide association study identifies new locus associated with OCD

By Nora I. Strom, Dongmei Yu, Zachary F Gerring, Matthew W. Halvorsen, Abdel Abdellaoui, Cristina Rodriguez-Fontenla, Julia M Sealock, Tim Bigdeli, Jonathan RI 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 Black, Michael Bloch, Julia Boberg, Rosa Bosch, Michael Breen, Brian P. Brennan, Helena Brentani, Joseph D. Buxbaum, Jonas Bybjerg-Grauholm, Enda M. Byrne, Beatriz Camarena, Adrian Camarena, Carolina Cappi, Angel Carracedo, Miguel Casas, Maria Cristina Cavallini, Valentina Ciullo, Edwin H. Cook, Vladimir Coric, Bernadette A. Cullen, Elles J De Schipper, Bernie Devlin, Srdjan Djurovic, Jason A. Elias, Lauren Erdman, Xavier Estivil, Martha J Falkenstein, Bengt T Fundin, Maiken E Gabrielsen, Fernando S Goes, Marco A Grados, Jakob Grove, Wei Guo, Jan Haavik, Kristen Hagen, Alexandra Havdahl, Ana G. Hounie, Donald Hucks, Christina Hultman, Magdalena Janecka, Michael Jenike, Elinor K Karlsson, Julia Klawohn, Lambertus Klei, Janice Krasnow, Kristi Krebs, Jason Krompinger, Nuria Lanzagorta, Fabio Macciardi, Brion Maher, 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, Teemu Palviainen, Fabrizio Piras, Federica Piras, Ann E Pulver, Raquel Rabionet Janssen, Alfredo Ramirez, Scott Rauch, Abraham Reichenberg, Jennifer Reichert, Mark A Riddle, Stephan Ripke, Aline S Sampaio, Miriam A. Schiele, Laura G Sloofman, Jan Smit, Janet L. Sobell, Maria Soler Artigas, Laurent F. Thomas, Homero Vallada, Jeremy Veenstra-VanderWeele, Nienke N.C.C. Vulink, Christopher P Walker, Ying Wang, Jens R. Wendland, Bendik S Winsvold, Yin Yao, Pino Alonso, Goetz Berberich, Cynthia Bulik, Danielle Cath, Daniele Cusi, Richard Delorme, Damiaan Denys, Valsamma Eapen, Peter Falkai, Thomas V Fernandez, Abby J Fyer, Daniel A Geller, Hans J Grabe, Benjamin D Greenberg, Gregory L Hanna, Ian Hickie, David M Hougaard, Norbert Kathmann, James Kennedy, Liang Kung-Yee, Mikael Landen, Stephanie Le Hellard, Marion Leboyer, Christine Lochner, James T. McCracken, Sarah. Medland, Preben B Mortensen, Benjamin M Neale, Humberto Nicolini, Merete Nordentoft, Michele Pato, Carlos Pato, David L Pauls, Nancy L. Pedersen, John Piacentini, Christopher Pittenger, Danielle Posthuma, Josep Antoni Ramos-Quiroga, Steven A Rasmussen, Kerry J Ressler, Margaret A Richter, Maria C Rosario, 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 Borglum, Susanne Walitza, Bjarne K A Hansen, Christian P Rueck, Nicholas G Martin, Lili Milani, Ole Mors, Ted Reichborn-Kjennerud, Marta Ribases, Gerd Kvale, David Mataix-Cols, Katharina Domschke, Edna Gruenblatt, Michael Wagner, John-Anker Zwart, Gerome Breen, Gerald Nestadt, Andres Metspalu, Jaakko Kaprio, Paul D 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

Posted 23 Oct 2021
medRxiv DOI: 10.1101/2021.10.13.21261078

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 substantial 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.

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