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

Publication ,  Journal Article
Strom, NI; Gerring, ZF; Galimberti, M; Yu, D; Halvorsen, MW; Abdellaoui, A; Rodriguez-Fontenla, C; Sealock, JM; Bigdeli, T; Coleman, JR; Bey, K ...
Published in: Nature genetics
June 2025

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.

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Published In

Nature genetics

DOI

EISSN

1546-1718

ISSN

1061-4036

Publication Date

June 2025

Volume

57

Issue

6

Start / End Page

1389 / 1401

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Obsessive-Compulsive Disorder
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Genetic Loci
  • Female
  • Developmental Biology
  • Case-Control Studies
 

Citation

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ICMJE
MLA
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Strom, N. I., Gerring, Z. F., Galimberti, M., Yu, D., Halvorsen, M. W., Abdellaoui, A., … Mattheisen, M. (2025). Genome-wide analyses identify 30 loci associated with obsessive-compulsive disorder. Nature Genetics, 57(6), 1389–1401. https://doi.org/10.1038/s41588-025-02189-z
Strom, Nora I., Zachary F. Gerring, Marco Galimberti, Dongmei Yu, Matthew W. Halvorsen, Abdel Abdellaoui, Cristina Rodriguez-Fontenla, et al. “Genome-wide analyses identify 30 loci associated with obsessive-compulsive disorder.Nature Genetics 57, no. 6 (June 2025): 1389–1401. https://doi.org/10.1038/s41588-025-02189-z.
Strom NI, Gerring ZF, Galimberti M, Yu D, Halvorsen MW, Abdellaoui A, et al. Genome-wide analyses identify 30 loci associated with obsessive-compulsive disorder. Nature genetics. 2025 Jun;57(6):1389–401.
Strom, Nora I., et al. “Genome-wide analyses identify 30 loci associated with obsessive-compulsive disorder.Nature Genetics, vol. 57, no. 6, June 2025, pp. 1389–401. Epmc, doi:10.1038/s41588-025-02189-z.
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, 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 J-A, 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. Nature genetics. 2025 Jun;57(6):1389–1401.

Published In

Nature genetics

DOI

EISSN

1546-1718

ISSN

1061-4036

Publication Date

June 2025

Volume

57

Issue

6

Start / End Page

1389 / 1401

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Obsessive-Compulsive Disorder
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Genetic Loci
  • Female
  • Developmental Biology
  • Case-Control Studies