Identifying Pediatric Mood Disorders From Transdiagnostic Polygenic Risk Scores

Abstract

Objective: Mood disorders often co-occur with attention deficit-hyperactive disorder (ADHD), disruptive behavior disorders (DBD), and aggression. We aimed to determine if polygenic risk scores (PRSs) based on external genome-wide association studies (GWASs) of these disorders could improve genetic prediction of mood disorders. Methods: We combined six independent family studies that had genetic data and diagnoses for mood disorders that were made using different editions of the DSM. We predict the onset of mood disorders in participants between 6 and 17 years of age using PRSs calculated using summary statistics of GWASs for ADHD, ADHD with DBD, major depressive disorder (MDD), bipolar disorder (BPD), and aggression to compute PRSs. Results: In our sample of 485 youths, 356 (73%) developed a subthreshold or full mood disorder and 129 (27%) did not. The cross-validated mean areas under the receiver operating characteristic curve (AUCs) for the seven models predicting development of any mood disorder ranged from 0.552 in the base model of age and sex to 0.648 in the base + all five PRSs model. When included in the base model individually, the ADHD PRS (OR=1.65, p<0.001), aggression PRS (OR=1.27, p=0.02), and MDD PRS (OR=1.23, p=0.047) were significantly associated with the development of any mood disorder. Conclusions: Using PRSs for ADHD, MDD, BPD, DBDs and aggression, we could modestly predict the development of mood disorders. These findings extend evidence for transdiagnostic genetic components of psychiatric illness and demonstrate that PRSs calculated using traditional diagnostic boundaries can be useful within a transdiagnostic framework.