Genetics and Epigenetics of Obsessive-Compulsive Disorder

Area of Science:

• Genetics and Genomics
• Neuroscience
• Psychiatry

Background:

• Obsessive-compulsive disorder (OCD) is a complex psychiatric condition with significant heritability.
• Previous genetic studies were limited by power and reproducibility.
• Recent large-scale genomic and multi-omic studies are advancing our understanding of OCD's genetic architecture.

Purpose of the Study:

• To synthesize current evidence from recent genomic and epigenomic studies on OCD.
• To explore the implications for molecular pathways in OCD pathogenesis.
• To integrate genetic findings with endophenotypic evidence.

Main Methods:

• Review of peer-reviewed literature and preprints.
• Focus on genome-wide association studies (GWAS), whole exome sequencing (WES), whole genome sequencing (WGS), and methylome-wide association studies (MWAS).
• Integration of genetic results with biochemical, physiological, structural, functional, and cognitive endophenotypes.

Main Results:

• Strong evidence for a polygenic contribution from common variants in OCD.
• Rare coding and structural variants also contribute, with signals enriched in neurodevelopmental pathways.
• Epigenomic studies show replicable methylation patterns, with potential sex-dependent effects.
• Cross-omics signals point to synaptic organization, neurodevelopment, chromatin regulation, immune/stress pathways, and cellular homeostasis.

Conclusions:

• OCD risk is best explained by an integrative model combining polygenic load, rare variants, and epigenetic mechanisms.
• These mechanisms influence intermediate phenotypes at circuit and cognitive levels.
• Findings may inform future research frameworks and personalized OCD treatment approaches, though not yet clinically applicable for diagnosis.