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

Strom, NI; Backman, J; Gerring, ZF; Borte, S; Galimberti, M; Hoffler, KD; Yu, D; Rosario, MC; Halvorsen, MW; Estonian, Biobank; Abdellaoui, A; andMe, Inc; Rodriguez-Fontenla, C; Landen, M; Sealock, JM; Borglum, AD; Bigdeli, T; Ruck, C; Coleman, JR; Ribases, M; Mahjani, B; Grunblatt, E; Thorp, JG; Bey, K; Burton, CL; Luykx, JJ; Zai, G; Alemany, S; Andre, C; Askland, KD; Banaj, N; Barlassina, C; Nissen, JB; Bienvenu, OJ; Black, D; Bloch, MH; 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; 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&#39;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; 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; 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; 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; Walitza, S; Hveem, K; Hansen, BK; Martin, NG; Milani, L; Mors, O; Reichborn-Kjennerud, T; Kvale, G; Mataix-Cols, D; Domschke, K; 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

Author(s): Strom, NI; Backman, J; Gerring, ZF; Borte, S; Galimberti, M; Hoffler, KD; Yu, D; Rosario, MC; Halvorsen, MW; Estonian, Biobank; Abdellaoui, A; andMe, Inc; Rodriguez-Fontenla, C; Landen, M; Sealock, JM; Borglum, AD; Bigdeli, T; Ruck, C; Coleman, JR; Ribases, M; Mahjani, B; Grunblatt, E; Thorp, JG; Bey, K; Burton, CL; Luykx, JJ; Zai, G; Alemany, S; Andre, C; Askland, KD; Banaj, N; Barlassina, C; Nissen, JB; Bienvenu, OJ; Black, D; Bloch, MH; 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; 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; 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; 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; 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; Walitza, S; Hveem, K; Hansen, BK; Martin, NG; Milani, L; Mors, O; Reichborn-Kjennerud, T; Kvale, G; Mataix-Cols, D; Domschke, K; 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;
Details: Publication Year 2025-06,Volume 57,Issue #6,Page 1389-1401
Journal Title: Nature Genetics
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.
Publisher: Springer Nature
Keywords: Humans; *Obsessive-Compulsive Disorder/genetics; *Genome-Wide Association Study; *Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Adult; Female; Male; *Genetic Loci; Case-Control Studies
Research Division(s): Genetics and Gene Regulation
PubMed ID: 40360802
Publisher's Version: https://doi.org/10.1038/s41588-025-02189-z
Open Access at Publisher's Site: https://doi.org/10.1038/s41588-025-02189-z
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-05-29 02:03:38

Last Modified: 2025-09-23 11:13:55