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

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 a...

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Authors: Strom, Nora I.|||0000-0002-5261-8852; Gerring, Zachary F.|||0000-0002-2445-1266; Galimberti, Marco|||0000-0001-6052-156X; Yu, Dongmei|||0000-0001-7901-4365; Halvorsen, Matthew W.|||0000-0002-6707-2418; Abdellaoui, Abdel|||0000-0003-1088-6784; Rodriguez-Fontenla, Cristina|||0000-0002-9829-6393; Sealock, Julia M.|||0000-0002-9346-3498; Bigdeli, Tim; Coleman, Jonathan R. I.|||0000-0002-6759-0944; Mahjani, Behrang|||0000-0001-6087-9537; Thorp, Jackson G.|||0000-0002-9461-6417; Bey, Katharina|||0000-0001-6392-4997; Burton, Christie L.|||0000-0002-8955-6528; Luykx, Jurjen J.|||0000-0002-6439-2774; Zai, Gwyneth|||0000-0002-0894-6867; Alemany, Sílvia|||0000-0002-7925-6767; Andre, Christine; Askland, Kathleen D.|||0000-0003-1467-8923; Bäckman, Julia; Banaj, Nerisa|||0000-0002-6317-8549; Barlassina, Cristina|||0000-0001-7407-2697; Nissen, Judith Becker|||0000-0003-4063-6866; Bienvenu, O. Joseph|||0000-0002-8466-102X; Black, Donald|||0000-0001-8038-1971; Bloch, Michael H.|||0000-0003-0352-4080; Børte, Sigrid|||0000-0001-9540-3256; Bosch, Rosa|||0000-0002-7596-183X; Breen, Michael; Brennan, Brian P.|||0000-0001-5468-6552; Brentani, Helena|||0000-0001-5192-4682; Buxbaum, Joseph D.|||0000-0001-8898-8313; Bybjerg-Grauholm, Jonas|||0000-0003-1705-4008; Byrne, Enda M.|||0000-0002-9491-7797; Cabana-Domínguez, Judit|||0000-0002-4732-7284; Camarena, Beatriz; Camarena, Adrian|||0000-0001-8512-0607; Cappi, Carolina|||0000-0001-6661-3756; Carracedo, Ángel|||0000-0003-1085-8986; Casas Brugué, Miquel|||0000-0003-3496-8522; Cavallini, Maria Cristina|||0000-0001-5913-1468; Ciullo, Valentina|||0000-0002-4095-7806; Cook, Edwin H.|||0000-0002-5848-5114; Crosby, Jesse; Cullen, Bernadette A.|||0000-0003-1762-092X; De Schipper, Elles J.|||0000-0001-9494-451X; Delorme, Richard|||0000-0002-5614-3663; Djurovic, Srdjan|||0000-0002-8140-8061; Elias, Jason A.; Estivill, Xavier|||0000-0002-0723-2256; Falkenstein, Martha J.|||0000-0001-5074-3409; Fundin, Bengt T.|||0000-0002-6037-7331; Garner, Lauryn; Gironda, Christina; Goes, Fernando S.|||0000-0001-6262-8264; Grados, Marco A.|||0000-0002-0178-1764; Grove, Jakob|||0000-0003-2284-5744; Guo, Wei|||0000-0002-4322-3699; Haavik, Jan|||0000-0001-7865-2808; Hagen, Kristen|||0000-0002-4286-1277; Harrington, Kelly|||0000-0001-9668-183X; Havdahl, Alexandra|||0000-0002-9268-0423; Höffler, Kira D.|||0000-0002-0837-1469; Hounie, Ana G.|||0000-0002-5026-2880; Hucks, Donald|||0000-0002-2700-5798; Hultman, Christina|||0000-0002-0327-2410; Janecka, Magdalena|||0000-0001-7406-0776; Jenike, Eric; Karlsson, Elinor K.|||0000-0002-4343-3776; Kelley, Kara; Klawohn, Julia|||0000-0002-9436-6948; Krasnow, Janice E.|||0000-0003-0316-6279; Krebs, Kristi|||0000-0003-0494-2751; Lange, Christoph|||0000-0002-9691-4741; Lanzagorta, Nuria|||0000-0001-6769-6813; Levey, Daniel|||0000-0001-8431-9569; Lindblad-Toh, Kerstin|||0000-0001-8338-0253; Macciardi, Fabio|||0000-0003-0537-4266; Maher, Brion|||0000-0001-9809-0064; Mathes, Brittany; McArthur, Evonne|||0000-0003-4566-4321; McGregor, Nathaniel|||0000-0001-7195-4993; McLaughlin, Nicole C.|||0000-0002-4016-2747; Meier, Sandra|||0000-0002-3287-5894; Miguel, Euripedes C.|||0000-0002-9393-3103; Mulhern, Maureen|||0000-0001-8642-4741; Nestadt, Paul S.; Nurmi, Erika L.|||0000-0003-4893-8957; O'Connell, Kevin S.|||0000-0002-6865-8795; Osiecki, Lisa|||0000-0002-9408-8722; Ousdal, Olga Therese|||0000-0002-0728-3141; Palviainen, Teemu|||0000-0002-7847-8384; Pedersen, Nancy L.|||0000-0001-8057-3543; Piras, Fabrizio|||0000-0003-3566-5494; Piras, Federica|||0000-0002-9546-7038; Potluri, Sriramya|||0000-0003-3877-0038; Rabionet, Raquel|||0000-0001-5006-8140; Ramirez, Alfredo|||0000-0003-4991-763X; Rauch, Scott|||0000-0001-7699-6754; Reichenberg, Abraham|||0000-0003-2729-8575; Riddle, Mark A.|||0000-0001-8764-2134; Ripke, Stephan|||0000-0003-3622-835X; Rosário, Maria C.|||0000-0002-8577-3306; Sampaio, Aline S.|||0000-0001-5568-6167; Schiele, Miriam A.|||0000-0003-2613-6515; Skogholt, Anne Heidi|||0000-0001-7466-0405; Sloofman, Laura G Sloofman G.|||0000-0001-7628-4378; Smit, Jan; Soler Artigas, María|||0000-0002-3213-1107; Thomas, Laurent|||0000-0003-0548-2486; Tifft, Eric|||0000-0002-7480-0276; Vallada, Homero|||0000-0001-5123-8295; van Kirk, Nathanial|||0000-0002-1975-4238; Veenstra-VanderWeele, Jeremy|||0000-0002-6349-1076; Vulink, Nienke N.|||0000-0001-8991-9627; Walker, Christopher P.|||0000-0002-6069-0184; Wang, Ying; Wendland, Jens|||0000-0001-5106-5013; Winsvold, Bendik Slagsvold|||0000-0003-4171-8919; Yao, Yin|||0000-0001-7487-4294; Zhou, Hang|||0000-0002-7694-6391; Agrawal, Arpana|||0000-0002-0313-793X; Alonso, Pino|||0000-0002-5779-9111; Berberich, Götz|||0000-0001-8300-9294; Bucholz, Kathleen K.|||0000-0003-3794-0736; Bulik, Cynthia M.|||0000-0001-7772-3264; Cath, Danielle|||0000-0001-9539-4118; Denys, Damiaan|||0000-0002-3191-3844; Eapen, Valsamma|||0000-0001-6296-8306; Edenberg, Howard J.|||0000-0003-0344-9690; Falkai, Peter|||0000-0003-2873-8667; Fernandez, Thomas V.|||0000-0003-0830-022X; Fyer, Abby J.|||0000-0002-0944-2505; Geller, Dan A.|||0000-0001-8692-4156; Grabe, Hans J.|||0000-0003-3684-4208; Greenberg, Benjamin D.|||0000-0002-5648-0002; Hanna, Gregory L.|||0000-0002-0742-6990; Hickie, Ian B.|||0000-0001-8832-9895; Hougaard, David M.|||0000-0001-5928-3517; Kathmann, Norbert|||0000-0002-1348-7060; Kennedy, James L.|||0000-0002-8733-3806; Lai, Dongbing|||0000-0001-7803-580X; Landén, Mikael|||0000-0002-4496-6451; Le Hellard, Stéphanie|||0000-0002-8085-051X; Leboyer, Marion|||0000-0001-5473-3697; Lochner, Christine|||0000-0002-4766-3704; McCracken, James T.|||0000-0003-0370-0777; Medland, Sarah Elizabeth|||0000-0003-1382-380X; Mortensen, Preben Bo|||0000-0002-5230-9865; Neale, Benjamin M.|||0000-0003-1513-6077; Nicolini, Humberto|||0000-0003-2494-0067; Nordentoft, Merete|||0000-0003-4895-7023; Pato, Michele; Pato, Carlos|||0000-0002-5858-266X; Pauls, David L.|||0000-0002-8107-345X; Piacentini, John|||0000-0003-4195-7194; Pittenger, Christopher|||0000-0003-2117-9321; Posthuma, Danielle|||0000-0001-7582-2365; Ramos-Quiroga, Josep Antoni|||0000-0003-1622-0350; Rasmussen, Steven A.|||0000-0002-8327-0692; Richter, Margaret A.|||0000-0001-5450-2936; Rosenberg, David R.|||0000-0002-0005-4151; Ruhrmann, Stephan|||0000-0002-6022-2364; Samuels, Jack F.|||0000-0002-6715-7905; Sandin, Sven|||0000-0001-6994-4884; Sandor, Paul|||0000-0003-2397-0758; Spalletta, Gianfranco|||0000-0002-7432-4249; Stein, Dan J.|||0000-0001-7218-7810; Stewart, S. Evelyn|||0000-0002-0994-6383; Storch, Eric A.|||0000-0002-7631-3703; Stranger, Barbara E.|||0000-0001-9021-7331; Turiel, Maurizio|||0000-0002-8793-2112; Werge, Thomas|||0000-0003-1829-0766; Andreassen, Ole A.|||0000-0002-4461-3568; Børglum, Anders D.|||0000-0001-8627-7219; Walitza, Susanne|||0000-0002-8161-8683; Hveem, Kristian|||0000-0001-8157-9744; Hansen, Bjarne K.|||0000-0001-5659-1119; Rück, Christian P.|||0000-0002-8742-0168; Martin, Nicholas G.|||0000-0003-4069-8020; Milani, Lili|||0000-0002-5323-3102; Mors, Ole|||0000-0002-5660-0393; Reichborn-Kjennerud, Ted|||0000-0003-4653-0034; Ribasés Haro, Marta|||0000-0003-1039-1116; Kvale, Gerd|||0000-0001-5449-2344; Mataix-Cols, David|||0000-0002-4545-0924; Domschke, Katharina|||0000-0002-2550-9132; Grünblatt, Edna|||0000-0001-8505-7265; Wagner, Michael; Zwart, John-Anker|||0000-0001-5721-0154; Breen, Gerome|||0000-0003-2053-1792; Nestadt, Gerald|||0000-0001-9461-5249; Kaprio, Jaakko|||0000-0002-3716-2455; Arnold, Paul D.|||0000-0003-2496-4624; Grice, Dorothy E.|||0000-0002-8833-2549; Knowles, James A.|||0000-0002-3307-5741; Ask, Helga|||0000-0003-0149-5319; Verweij, Karin|||0000-0001-9868-7821; Davis, Lea K.|||0000-0001-5143-2282; Smit, Dirk J.|||0000-0001-8301-8860; Crowley, James J.|||0000-0001-9051-1557; Scharf, Jeremiah M.|||0000-0002-4742-5896; Stein, Murray B.|||0000-0001-9564-2871; Gelernter, Joel|||0000-0002-4067-1859; Mathews, Carol A.|||0000-0003-2208-7058; Derks, Eske M.|||0000-0002-6292-6883; Mattheisen, Manuel|||0000-0002-8442-493X
Format: Article
Publication date:2025
Country:España
Institution:Universitat Autònoma de Barcelona
Repository:Dipòsit Digital de Documents de la UAB
Language:English
OAI Identifier:oai:dnet:uabarcelona_::726682f1b8552173ca088a4f4781aa68
Online Access:https://ddd.uab.cat/record/327781
https://dx.doi.org/urn:doi:10.1038/s41588-025-02189-z
Access Level:Open access
Description
Summary: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 and D 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.