Shared Transethnic Genetic Basis Between Panic Disorder and Psychiatric and Intermediate Phenotypes

Abstract

Panic disorder (PD) is modestly heritable. The genetic basis of anxiety disorders overlaps with that of other psychiatric disorders and their intermediate phenotypes in individuals of European ancestry. Here, we investigated the transethnic polygenetic features shared between Japanese PD patients and European patients with psychiatric disorders and their intermediate phenotypes by conducting polygenic risk score (PRS) analyses. Large-scale European genome-wide association study (GWAS) datasets for psychiatric disorders and intermediate phenotypes were utilized as discovery samples. PRSs derived from these GWASs were calculated for Japanese target subjects [PD patients and healthy controls (HCs) ].The effects of these PRSs from European GWASs on the risk of PD in Japanese patients were investigated. The PRSs from European studies of anxiety disorders were significantly higher in Japanese PD patients than in HCs. Of other psychiatric disorders, the PRSs for depression in European patients were significantly higher in Japanese PD patients than in HCs, while the PRSs for attention-deficit/hyperactivity disorder in European patients were nominally lower in Japanese PD patients than in HCs. Of intermediate phenotypes, the PRSs for loneliness in European individuals were significantly higher in Japanese PD patients than in HCs. Furthermore, Japanese PD patients scored nominally higher than HCs in PRSs for neuroticism in European people, while Japanese PD patients scored nominally lower than HCs in PRSs for tiredness, educational attainment and cognitive function. Our findings suggest that PD shares transethnic genetic etiologies with other psychiatric disorders and related intermediate phenotypes.