F31. POLYGENIC RISK SCORES AND EARLY RISK ENDOPHENOTYPES IN CHILDREN AT GENETIC RISK OF SCHIZOPHRENIA AND BIPOLAR DISORDER: IMPLICATIONS FOR THE DEFINITION OF THE CHILDHOOD RISK STATUS

摘要

BackgroundPolygenic risk scores (PRS) of schizophrenia (SZ) or bipolar disorder (BD) are derived from genomewide association studies discriminating unrelated patients from controls. We have recently shown that both the SZ PRS and the BD PRS also distinguished affected patients from their non-affected adult relatives in a familial sample.1 Furthermore, the association of the SZ PRS with BD subjects and, reciprocally, of the BD PRS with SZ subjects support the shared susceptibility for these diseases.1 Importantly, new studies suggest that PRS would also distinguish the offspring at genetic risk from controls2 and may be associated with psychotic-like experiences and negative symptoms in adolescents of the general population.3 Little is known though about the contribution of the PRS in the risk prediction in children at genetic risk.Our group and others have shown that the risk trajectory of high-risk children (HR) born to an affected parent can be characterized by their risk endophenotypes, i.e. specific cognitive deficits and psychotic-like or mood-like experiences in childhood that flag the neurodevelopmental origin of the illness. Children at risk accumulate these risk endophenotypes along their developmental trajectory and this aggregation is a predictor of later transition to illness.4,5We hypothesized that since the PRS is a reflection of the genomic liability to illness, it would consequently relate to risk endophenotypes and their aggregation in children at risk. Our objectives were to evaluate i) the power of PRS to discriminate children at risk from healthy controls and, ii) the association of SZ and BP PRS to early risk endophenotypes in these children.