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

Nora I Strom; Zachary F Gerring; Marco Galimberti; Dongmei Yu; Matthew Halvorsen; Abdel Abdellaoui; Cristina Rodriguez‐Fontenla; Julia Sealock; Tim Bigdeli; Jonathan R Coleman; Behrang Mahjani; Jackson G Thorp; Katharina Bey; Christie L Burton; Jurjen J Luykx; Gwyneth Zai; Silvia Alemany; Christine Andre; Kathleen D. Askland; Julia Bäckman; Nerisa Banaj; Cristina Barlassina; Judith Becker Nissen; O Joseph Bienvenu; Donald W. Black; Michael H. Bloch; Sigrid Børte; Rosa Bosch; Michael Breen; Brian P Brennan

doi:10.1038/s41588-025-02189-z

Genetic & Genomic MedicineResearch at the University of Copenhagen (University of Copenhagen)Jan 1, 2025

Peer-reviewed journal article

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

Nora I Strom, Zachary F Gerring, Marco Galimberti, Dongmei Yu iD, Matthew Halvorsen iD, Abdel Abdellaoui iD, Cristina Rodriguez‐Fontenla iD, Julia Sealock iD, Tim Bigdeli, Jonathan R Coleman iD, Behrang Mahjani iD, Jackson G Thorp, Katharina Bey iD, Christie L Burton, Jurjen J Luykx, Gwyneth Zai, Silvia Alemany iD, Christine Andre, Kathleen D. Askland iD, Julia Bäckman, Nerisa Banaj iD, Cristina Barlassina iD, Judith Becker Nissen iD, O Joseph Bienvenu, Donald W. Black iD, , Bjarne K. A. Hansen iD

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, CTNND1 and multiple genes in the 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 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 of 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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