The polygenic risk for obsessive-compulsive disorder is associated with the personality trait harm avoidance

Area of Science:

• Psychiatry
• Genetics
• Behavioral Science

Background:

• Obsessive-compulsive disorder (OCD) has a significant genetic component, though specific genetic variants remain elusive.
• Genome-wide association studies (GWAS) highlight the role of common single nucleotide polymorphisms (SNPs) in OCD's heritability.
• Understanding gene-to-phenotype pathways requires investigating genetic liability, such as polygenic risk scores (PRS), alongside potential endophenotypes like harm avoidance.

Purpose of the Study:

• To investigate the association between the genetic liability for OCD, quantified by PRS, and the personality trait of harm avoidance.
• To explore harm avoidance as a potential endophenotype for OCD.
• To elucidate functional pathways connecting genetic risk to OCD phenotypes.

Main Methods:

• Derived PRS for OCD using data from the Psychiatric Genomics Consortium OCD GWAS.
• Utilized an independent sample comprising OCD patients, their unaffected first-degree relatives, and healthy controls.
• Employed linear regression and mediation analyses to assess the relationship between OCD PRS and harm avoidance.

Main Results:

• OCD PRS significantly predicted OCD status, with patients exhibiting the highest scores and relatives showing intermediate scores.
• A significant association was found between genetic risk for OCD and harm avoidance in the overall sample and within the OCD patient group.
• Mediation analyses confirmed that harm avoidance mediates the link between OCD PRS and OCD caseness, consistent across multiple P-value thresholds and after excluding comorbid conditions.

Conclusions:

• The findings support the polygenic architecture of OCD.
• Harm avoidance is validated as a candidate endophenotype and diathesis for OCD.
• This research enhances understanding of the genetic underpinnings and phenotypic expression of OCD.