Genome-wide analyses identify 30 loci associated with obsessive-compulsive disorder
Strom, Nora I ; Gerring, Zachary F ; Galimberti, Marco ; Yu, Dongmei ; Halvorsen, Matthew W ; Abdellaoui, Abdel ; Rodriguez-Fontenla, Cristina ; Sealock, Julia M ; Bigdeli, Tim ; Coleman, Jonathan R ... show 10 more
Authors
Gerring, Zachary F
Galimberti, Marco
Yu, Dongmei
Halvorsen, Matthew W
Abdellaoui, Abdel
Rodriguez-Fontenla, Cristina
Sealock, Julia M
Bigdeli, Tim
Coleman, Jonathan R
Mahjani, Behrang
Thorp, Jackson G
Bey, Katharina
Burton, Christie L
Luykx, Jurjen J
Zai, Gwyneth
Alemany, Silvia
Andre, Christine
Askland, Kathleen D
Bäckman, Julia
Banaj, Nerisa
Barlassina, Cristina
Nissen, Judith Becker
Bienvenu, O Joseph
Black, Donald
Bloch, Michael H
Børte, Sigrid
Bosch, Rosa
Breen, Michael
Brennan, Brian P
Brentani, Helena
Buxbaum, Joseph D
Bybjerg-Grauholm, Jonas
Byrne, Enda M
Cabana-Dominguez, Judit
Camarena, Beatriz
Camarena, Adrian
Cappi, Carolina
Carracedo, Angel
Casas, Miguel
Cavallini, Maria Cristina
Ciullo, Valentina
Cook, Edwin H
Crosby, Jesse
Cullen, Bernadette A
De Schipper, Elles J
Delorme, Richard
Djurovic, Srdjan
Elias, Jason A
Estivill, Xavier
Falkenstein, Martha J
Fundin, Bengt T
Garner, Lauryn
Gironda, Christina
Goes, Fernando S
Grados, Marco A
Grove, Jakob
Guo, Wei
Haavik, Jan
Hagen, Kristen
Harrington, Kelly
Havdahl, Alexandra
Höffler, Kira D
Hounie, Ana G
Hucks, Donald
Hultman, Christina
Janecka, Magdalena
Jenike, Eric
Karlsson, Elinor K
Kelley, Kara
Klawohn, Julia
Krasnow, Janice E
Krebs, Kristi
Lange, Christoph
Lanzagorta, Nuria
Levey, Daniel
Lindblad-Toh, Kerstin
Macciardi, Fabio
Maher, Brion
Mathes, Brittany
McArthur, Evonne
McGregor, Nathaniel
McLaughlin, Nicole C
Meier, Sandra
Miguel, Euripedes C
Mulhern, Maureen
Nestadt, Paul S
Nurmi, Erika L
O'Connell, Kevin S
Osiecki, Lisa
Ousdal, Olga Therese
Palviainen, Teemu
Pedersen, Nancy L
Piras, Fabrizio
Piras, Federica
Potluri, Sriramya
Rabionet, Raquel
Ramirez, Alfredo
Rauch, Scott
Reichenberg, Abraham
Riddle, Mark A
Ripke, Stephan
Rosário, Maria C
Sampaio, Aline S
Schiele, Miriam A
Skogholt, Anne Heidi
Sloofman, Laura G
Smit, Jan
Artigas, María Soler
Thomas, Laurent F
Tifft, Eric
Vallada, Homero
van Kirk, Nathanial
Veenstra-VanderWeele, Jeremy
Vulink, Nienke N
Walker, Christopher P
Wang, Ying
Wendland, Jens R
Winsvold, Bendik S
Yao, Yin
Zhou, Hang
Agrawal, Arpana
Alonso, Pino
Berberich, Götz
Bucholz, Kathleen K
Bulik, Cynthia M
Cath, Danielle
Denys, Damiaan
Eapen, Valsamma
Edenberg, Howard
Falkai, Peter
Fernandez, Thomas V
Fyer, Abby J
Gaziano, J M
Geller, Dan A
Grabe, Hans J
Greenberg, Benjamin D
Hanna, Gregory L
Hickie, Ian B
Hougaard, David M
Kathmann, Norbert
Kennedy, James
Lai, Dongbing
Landén, Mikael
Hellard, Stéphanie Le
Leboyer, Marion
Lochner, Christine
McCracken, James T
Medland, Sarah E
Mortensen, Preben B
Neale, Benjamin M
Nicolini, Humberto
Nordentoft, Merete
Pato, Michele
Pato, Carlos
Pauls, David L
Piacentini, John
Pittenger, Christopher
Posthuma, Danielle
Ramos-Quiroga, Josep Antoni
Rasmussen, Steven A
Richter, Margaret A
Rosenberg, David R
Ruhrmann, Stephan
Samuels, Jack F
Sandin, Sven
Sandor, Paul
Spalletta, Gianfranco
Stein, Dan J
Stewart, S Evelyn
Storch, Eric A
Stranger, Barbara E
Turiel, Maurizio
Werge, Thomas
Andreassen, Ole A
Børglum, Anders D
Walitza, Susanne
Hveem, Kristian
Hansen, Bjarne K
Rück, Christian
Martin, Nicholas G
Milani, Lili
Mors, Ole
Reichborn-Kjennerud, Ted
Ribasés, Marta
Kvale, Gerd
Mataix-Cols, David
Domschke, Katharina
Grünblatt, Edna
Wagner, Michael
Zwart, John-Anker
Breen, Gerome
Nestadt, Gerald
Kaprio, Jaakko
Arnold, Paul D
Grice, Dorothy E
Knowles, James A
Ask, Helga
Verweij, Karin J
Davis, Lea K
Smit, Dirk J
Crowley, James J
Scharf, Jeremiah M
Stein, Murray B
Gelernter, Joel
Mathews, Carol A
Derks, Eske M
Mattheisen, Manuel
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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 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.
Source
Strom NI, Gerring ZF, Galimberti M, Yu D, Halvorsen MW, Abdellaoui A, Rodriguez-Fontenla C, Sealock JM, Bigdeli T, Coleman JR, Mahjani B, Thorp JG, Bey K, Burton CL, Luykx JJ, Zai G, Alemany S, Andre C, Askland KD, Bäckman J, Banaj N, Barlassina C, Nissen JB, Bienvenu OJ, Black D, Bloch MH, Børte S, Bosch R, Breen M, Brennan BP, Brentani H, Buxbaum JD, Bybjerg-Grauholm J, Byrne EM, Cabana-Dominguez J, Camarena B, Camarena A, Cappi C, Carracedo A, Casas M, Cavallini MC, Ciullo V, Cook EH, Crosby J, Cullen BA, De Schipper EJ, Delorme R, Djurovic S, Elias JA, Estivill X, Falkenstein MJ, Fundin BT, Garner L, Gironda C, Goes FS, Grados MA, Grove J, Guo W, Haavik J, Hagen K, Harrington K, Havdahl A, Höffler KD, Hounie AG, Hucks D, Hultman C, Janecka M, Jenike E, Karlsson EK, Kelley K, Klawohn J, Krasnow JE, Krebs K, Lange C, Lanzagorta N, Levey D, Lindblad-Toh K, Macciardi F, Maher B, Mathes B, McArthur E, McGregor N, McLaughlin NC, Meier S, Miguel EC, Mulhern M, Nestadt PS, Nurmi EL, O'Connell KS, Osiecki L, Ousdal OT, Palviainen T, Pedersen NL, Piras F, Piras F, Potluri S, Rabionet R, Ramirez A, Rauch S, Reichenberg A, Riddle MA, Ripke S, Rosário MC, Sampaio AS, Schiele MA, Skogholt AH, Sloofman LG, Smit J, Artigas MS, Thomas LF, Tifft E, Vallada H, van Kirk N, Veenstra-VanderWeele J, Vulink NN, Walker CP, Wang Y, Wendland JR, Winsvold BS, Yao Y, Zhou H; Estonian Biobank; 23andMe Inc.; Agrawal A, Alonso P, Berberich G, Bucholz KK, Bulik CM, Cath D, Denys D, Eapen V, Edenberg H, Falkai P, Fernandez TV, Fyer AJ, Gaziano JM, Geller DA, Grabe HJ, Greenberg BD, Hanna GL, Hickie IB, Hougaard DM, Kathmann N, Kennedy J, Lai D, Landén M, Hellard SL, Leboyer M, Lochner C, McCracken JT, Medland SE, Mortensen PB, Neale BM, Nicolini H, Nordentoft M, Pato M, Pato C, Pauls DL, Piacentini J, Pittenger C, Posthuma D, Ramos-Quiroga JA, Rasmussen SA, Richter MA, Rosenberg DR, Ruhrmann S, Samuels JF, Sandin S, Sandor P, Spalletta G, Stein DJ, Stewart SE, Storch EA, Stranger BE, Turiel M, Werge T, Andreassen OA, Børglum AD, Walitza S, Hveem K, Hansen BK, Rück C, Martin NG, Milani L, Mors O, Reichborn-Kjennerud T, Ribasés M, Kvale G, Mataix-Cols D, Domschke K, Grünblatt E, Wagner M, Zwart JA, Breen G, Nestadt G, Kaprio J, Arnold PD, Grice DE, Knowles JA, Ask H, Verweij KJ, Davis LK, Smit DJ, Crowley JJ, Scharf JM, Stein MB, Gelernter J, Mathews CA, Derks EM, Mattheisen M. Genome-wide analyses identify 30 loci associated with obsessive-compulsive disorder. Nat Genet. 2025 May 13. doi: 10.1038/s41588-025-02189-z. Epub ahead of print. PMID: 40360802.
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This article is based on a previously available preprint in medRxiv, https://doi.org/10.1101/2024.03.13.24304161.