T23 - Polygenic Risk Scores Derived From Largest Schizophrenia Gwas Are Associated With The Presence Of Psychosis And Level Of Mood Incongruent Psychosis In Bipolar Disorder

Abstract

Background Bipolar disorder (BD) includes a broad range of phenotypic features – most research examining its genetic underpinning focuses on the overall syndrome rather than its subphenotypic components. BD is a highly heritable disorder and while its genetic architecture is not fully elucidated there is increasingly strong support for a very polygenic component with partial polygenic overlap with schizophrenia (SZ). Here we present preliminary results from an analysis examining the association of SZ derived polygenic risk scores (PRS) across different BD subtypes (Bipolar Type 1(BPI), Bipolar Type 2 (BPII) and Schizoaffective disorder (SAD), and subphenotypes defined by the presence of psychosis and its associated level of mood incongruence. Methods We used a UK sample of 3101 BP cases, collected using a consistently administrated interview protocol with OPCRIT confirmed lifetime diagnosis of Research Diagnostic Criteria (RDC - BPI, BPII or SAD). PRS were generated using 1000 genomes (phase3, 2014) imputed genetic data (INFO score>0.8, HWE>1e-6, MAF>0.01) trained on the results from Psychiatric Genetic Consortium (PGC2) SZ GWAS, pruned r2 Results PRS with the SZ association p-value cut-off of 0.5, have shown significant association across the BD subtypes with relative risk ratios RRR = 1.28 (95%CI: 1.18-1.39, p Discussion Preliminary analyses show a genetic - phenotypic association, between polygenic features of schizophrenia and BP characterised by the presence of psychosis, suggesting the phenotypic overlap between SZ and BD may in part be driven by polygenic overlap. This finding is further supported by the association of PRS and level of mood incongruence in the content of psychotic symptoms. These results suggest the PRS effect is not solely mediated though the psychosis subphenotype, at least in the BPI group. Our analyses show promise for the strategy of examining polygenic/phenotypic associations based on fine grained clinical characterisations