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

Area of Science:

• Genetics
• Neuroscience
• Psychiatry

Background:

• Obsessive-compulsive disorder (OCD) affects approximately 1% of the population.
• Genetic factors play a significant role in the etiology of OCD.

Purpose of the Study:

• To identify genetic loci associated with obsessive-compulsive disorder (OCD).
• To investigate the genetic architecture and shared genetic risks of OCD with other phenotypes.

Main Methods:

• Conducted a genome-wide association study (GWAS) meta-analysis of 53,660 OCD cases and 2,044,417 controls.
• Utilized gene-based approaches to identify potential effector genes.
• Estimated the number of genetic variants contributing to OCD heritability.

Main Results:

• Identified 30 independent genome-wide significant loci for OCD.
• Pinpointed 249 potential effector genes, with 25 identified as likely causal candidates, including WDR6, DALRD3, CTNND1, and MHC region genes.
• Estimated that approximately 11,500 genetic variants explain 90% of OCD heritability.
• Found OCD genetic risk associated with excitatory neurons in the hippocampus and cortex, and dopamine receptor-containing medium spiny neurons.
• Observed shared genetic risk between OCD and 65 other phenotypes, including psychiatric disorders like anxiety, depression, anorexia nervosa, and Tourette syndrome.
• Identified negative genetic correlations between OCD and inflammatory bowel diseases, educational attainment, and body mass index.

Conclusions:

• This study significantly expands the understanding of the genetic underpinnings of OCD.
• The findings highlight the role of specific neuronal populations and dopamine pathways in OCD.
• Genetic risk for OCD is substantially shared with other psychiatric conditions, suggesting common biological pathways.