Polygenic risk scores and the prediction of onset of mood and psychotic disorders in adolescents and young adults.

Abstract

To examine whether polygenic risk scores (PRS) for neuroticism, depression, bipolar disorder and schizophrenia are higher in individuals manifesting trans-diagnostic risk factors for the development of major mental disorders and whether PRS enhance prediction of early onset full-threshold disorders. Using data from the Brisbane Longitudinal Twin Study, we examined individual PRS for neuroticism, depression, bipolar disorder and schizophrenia, recorded evidence of subthreshold syndromes and family history of mood and/or psychotic disorders and noted progression to trans-diagnostic clinical caseness (onset of major mental disorders) at follow-up. We undertook multivariate, receiver operating curve and logistic regression analyses that were adjusted for known variables of influence (age, twin status, and so on). Of 1473 eligible participants (female = 866, 59%; mean age 26.3 years), 28% (n = 409) met caseness criteria for a mood and/or psychotic disorder. All PRS were higher in cases versus non-cases but associations with different levels of risk were inconsistent. The prediction of caseness (reported as area under the curve with 95% confidence intervals [CI]) improved from 0.68 (95% CI: 0.65, 0.71) when estimated using clinical risk factors alone up to 0.71 (95% CI: 0.69, 0.73) when PRS were added to the model. Logistic regression identified five variables that optimally classified individuals according to caseness: age, sex, individual risk characteristics, PRS for depression and mental health case status of cotwins or siblings. The findings need replication. However, this exploratory study suggests that combining PRS with other risk factors has the potential to improve outcome prediction in youth.