Center for Medical Ethics and Health Policy Staff Publications
Publication Date
6-1-2025
Journal
Nature Genetics
DOI
10.1038/s41588-025-02189-z
PMID
40360802
PMCID
PMC12165847
PubMedCentral® Posted Date
5-13-2025
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Humans, Obsessive-Compulsive Disorder, Genome-Wide Association Study, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Adult, Female, Male, Genetic Loci, Case-Control Studies, Genome-wide association studies, Genetics research
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