Autor:innen:
Katharina Bey, Bonn (Germany)
Leonie Weinhold, Bonn (Germany)
Rosa Grützmann, Berlin (Germany)
Stephan Heinzel, Berlin (Germany)
Christian Kaufmann, Berlin (Germany)
Julia Klawohn, Berlin (Germany)
Anja Riesel, Berlin (Germany)
Matthias Schmid, Bonn (Germany)
Alfredo Ramirez, Köln (Germany)
Norbert Kathmann, Berlin (Germany)
Michael Wagner, Bonn (Germany)
Obsessive-compulsive disorder (OCD) is a complex psychiatric disorder with a substantial genetic contribution. While the specific variants underlying OCD’s heritability are largely unknown, findings from GWAS corroborate the importance of common SNPs explaining the phenotypic variance in OCD. Investigating associations between the genetic liability for OCD, as reflected by polygenic risk scores, and promising candidate endophenotypes, such as the personality trait harm avoidance, may aid the understanding of functional pathways from genes to diagnostic phenotypes. Here, we calculated polygenic risk scores for OCD based on the latest PGC OCD GWAS and used linear regression to test whether polygenic scores are associated with harm avoidance in a sample of OCD patients (n = 180), their unaffected first-degree relatives (n = 108) and healthy controls (n = 200). OCD polygenic risk scores significantly predicted OCD status (p < 0.001 at pT = 0.3), with patients having the highest scores and relatives having intermediate scores. Furthermore, the genetic risk for OCD was associated with harm avoidance across the entire sample (p = 0.002 at pT = 0.3), and among OCD patients (p = .021 at pT = 0.1). These results were observed at multiple p-value thresholds, and persisted after the exclusion of patients with a current comorbid major depressive disorder. In male patients, we also found a significant association between polygenic risk scores and an earlier age of onset (p = .036 at pT = 0.5), which is in line with reports of male predominance and increased familiarity in early-onset OCD. There were no significant associations between polygenic risk scores and OCD symptom severity and symptom dimensions. Our findings support the validity of harm avoidance as an endophenotype of OCD and point to common genetic underpinnings. Harm avoidance may partially mediate the familial risk for OCD, representing a central vulnerability factor in the etiology of the disease.