M26 - THE IMPACT OF BIPOLAR AND SCHIZOPHRENIA POLYGENIC RISK SCORES ON FAMILIAL FEATURES OF BIPOLAR DISORDER

Abstract

Background In Bipolar Disorder (BD), some endophenotypes such as the occurrence of psychotic symptoms or suicide attempts, the level of psychosocial functioning, disorder subphenotypes like type I/II disorder and comorbidities like alcohol or drug abuse are highly familial. We explored whether polygenic risk scores for bipolar disorder (BD-PRS) or schizophrenia (SZ-PRS) can predict these phenotypes in a sample of German and Austrian patients diagnosed with BD according to DSM-IV-criteria. Methods The present study included 326 BD patients belonging to the German KFO/PsyCourse cohort (www.kfo241.de; www.PsyCourse.de). The study protocol was approved by the local ethics committees and is in accordance with the 1964 Declaration of Helsinki. Sociodemographic and clinical information on patients was assessed using a comprehensive inventory for phenotype characterization. Association of BD- and SZ-PRS with target variables was tested via logistic regression analyses at several inclusion p-value thresholds (0.00000005 to 1). Polygenic risk scores were calculated using imputed, quality-controlled genome-wide patient genotypes (Illumina Infinium PsychArray) and summary statistics of two large case-control genome-wide association studies (Hou et al., 2016; PGC-Schizophrenia-Working-Group, 2014). Results were corrected for age, sex, recruitment center, duration of illness and population stratification. Results A higher SZ polygenic burden was significantly associated with lifetime use of illicit drugs at several p-value thresholds (strongest association at threshold 0.0001, R2 change 2.7%, p-value=0.005). Only with one threshold a slightly positive association of SZ-PRS with alcohol abuse was observed (0.0000001, R2change 3.1%, p=0.026). Patients diagnosed with bipolar I disorder had higher SZ-PRS compared to patients with bipolar II disorder at several thresholds (strongest association at 0.05 threshold, R2 change= 2.4%, p=0.020, OR=1,6). We found no significant association of SZ-PRS with other target variables. Higher BD-PRS were significantly associated with higher levels of psychosocial functioning in our patient sample (measured by Global-Assessment-of-Functioning-scores, strongest effect at threshold 0.001, R2 change= 2.6%, p=0.014,), but not with any other target variable. Discussion Our results suggest that a higher polygenic SZ burden plays a bigger role for lifetime occurrence of substance abuse in BD patients than the polygenic BD burden. Also, there may be a stronger genetic overlap between schizophrenia and BD I disorder subtype than between schizophrenia and BD II disorder subtype. Interestingly, a higher polygenic BD burden may even have positive effects on overall psychosocial functioning in BD patients.