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

Abstract

The polygenic risk for obsessive-compulsive disorder is associated with the personality trait harm avoidance. Objective: Obsessive-compulsive disorder (OCD) is a complex psychiatric disorder with a substantial genetic contribution. While the specific variants underlying OCD's heritability are still unknown, findings from genome-wide association studies (GWAS) corroborate the importance of common SNPs explaining the phenotypic variance in OCD. Investigating associations between the genetic liability for OCD, as reflected by a polygenic risk score (PRS), and potential endophenotypes of the disorder, such as the personality trait harm avoidance, may aid the understanding of functional pathways from genes to diagnostic phenotypes. Methods: We derived PRS for OCD at several P-value thresholds based on the latest Psychiatric Genomics Consortium OCD GWAS (2688 cases, 7037 controls) in an independent sample of OCD patients (n = 180), their unaffected first-degree relatives (n = 108) and healthy controls (n = 200). Using linear regression, we tested whether these PRS are associated with the personality trait harm avoidance. Results: Results showed that OCD PRS significantly predicted OCD status, 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, and among OCD patients. As indicated by mediation analyses, harm avoidance mediated the association between the OCD PRS and OCD caseness. These results were observed at multiple P-value thresholds and persisted after the exclusion of patients with a current comorbid major depressive or anxiety disorder. Conclusion: Our findings support the polygenic nature of OCD and further validate harm avoidance as a candidate endophenotype and diathesis of OCD.

Metacognition and the effect of incentive motivation in two compulsive disorders: gambling disorder and obsessive-compulsive disorder

“…On the one hand, prospects of high monetary incentives could exaggerate overconfidence in GD patients, leading to continuation of compulsive gambling. On the other hand, in OCD this could lead to exaggerated decreased confidence in negative value context as harm avoidance is considered one of the core motivations of compulsive behavior in OCD [33][34][35] .…”

“…On the one hand, prospects of high monetary incentives could exaggerate general overconfidence in GD patients. On the other hand, as harm avoidance is considered one of the core motivations of compulsive behavior in OCD (Bey et al, 2017(Bey et al, , 2020Summerfeldt et al, 2014), this could drive an overall decreased confidence, which is specifically exaggerated in negative value contexts in OCD patients.…”

Dissecting the genetic architecture of suicide attempt and repeated attempts in Korean patients with bipolar disorder using polygenic risk scores

“…Neurocognitive deficits could be a potential mediator given that individuals with OCD and those with suicidal behavior showed similar patterns of impairment in executive function such as response inhibition, cognitive flexibility, and decision-making (Chamberlain et al 2007 ; Menzies et al 2007 ; Cavedini et al 2010 ; Rajender et al 2011 ; Bredemeier and Miller 2015 ; Zhang et al 2015 ; Ozcan et al 2016 ; Harfmann et al 2019 ). Moreover, in a recent study, PRS-OCD was associated with the personality trait of harm-avoidance (Bey et al 2020 ), which was suggested as a risk factor for SA in patients with BD (Engström et al 2004 ).…”

Polygenic risk for obsessive-compulsive disorder (OCD) predicts brain response during working memory task in OCD, unaffected relatives, and healthy controls

“…Linear regression analyses were performed to test associations between OCD polygenic risk scores and working memory performance. Note that, in line with previous reports including polygenic risk scores in related participants 34 , 35 , population structure covariates were included 28 in all analyses that involved polygenic risk scores.…”