Genome-wide association study identifies new loci associated with OCD

Area of Science:

• Genetics
• Psychiatry
• Neuroscience

Background:

• Previous genome-wide association studies (GWAS) for obsessive-compulsive disorder (OCD) identified limited significant single-nucleotide polymorphisms (SNPs) despite high heritability.
• A larger sample size is crucial for identifying more genetic factors and biological pathways influencing OCD susceptibility.

Approach:

• Conducted a large GWAS meta-analysis combining six cohorts and self-report data, significantly increasing case numbers (N=37,015) and controls (N=948,616).
• Performed gene-based tests, tissue/cell-type enrichment analyses, and heritability estimations.
• Utilized multivariable GWAS (MTAG) to explore genetic heterogeneity and identify additional significant SNPs.

Key Points:

• Identified 15 independent genome-wide significant loci (14 novel) and 79 protein-coding genes associated with OCD.
• Tissue enrichment implicated cortical regions, amygdala, and hypothalamus; cell type analysis highlighted 12 neuronal types.
• Estimated SNP-based heritability at 0.08 and found genetic correlations with 40 traits, including positive links to psychiatric disorders and negative links to BMI and autoimmune diseases.

Conclusions:

• This comprehensive GWAS meta-analysis significantly advances the understanding of OCD's genetic architecture.
• Identified key biological pathways and genes contributing to OCD etiology.
• Provides a foundation for future research into the biological mechanisms underlying OCD.