Exploring genetic variants in obsessive compulsive disorder severity: A GWAS approach

Area of Science:

• Genetics
• Psychiatry
• Neuroscience

Background:

• Obsessive-Compulsive Disorder (OCD) exhibits significant inter-individual variability in severity.
• Previous research indicated a polygenic risk score for OCD predicts treatment outcomes.
• The genetic basis of OCD severity remains largely unexplored.

Purpose of the Study:

• To investigate the genomic factors associated with OCD severity.
• To identify specific single-nucleotide polymorphisms (SNPs) and genes linked to variations in OCD symptom intensity.

Main Methods:

• Utilized the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) to quantify OCD severity in 401 patients.
• Employed the Infinium PsychArray-24 BeadChip kit for genotyping.
• Conducted linear regression analyses at both SNP and gene levels, including rare variants, followed by enrichment analyses.

Main Results:

• No SNPs met the stringent genome-wide significance threshold (p < 10^-8) for association with Y-BOCS scores.
• Six markers displayed suggestive associations (p < 10^-5), with the top SNP (rs7578149) located intergenically on chromosome 2.
• Gene enrichment analyses identified associations between OCD-related genes and porin activity (FDR = 0.01) and transmembrane structure (FDR = 0.04).

Conclusions:

• This study provides preliminary insights into the genetic architecture of OCD severity.
• Identified suggestive genetic loci and biological pathways potentially influencing OCD symptom intensity.
• Findings contribute to a more individualized understanding of OCD, potentially informing prognosis and treatment strategies.