Abstract

BackgroundSchizophrenia negatively impacts quality of life (QoL). A handful of variables from small studies have been reported to influence QoL of schizophrenia patients, but a study comprehensively dissecting the genetic and non-genetic contributing factors to QoL in these patients is currently lacking. We adopted a hypothesis-generating approach to assess the phenotypic and genotypic determinants of QoL in schizophrenia.\n\nMethodThe study population consisted of 1,119 patients with a psychotic disorder, 1,979 relatives and 586 healthy controls. Using linear regression, we tested >100 independent demographic, cognitive and clinical phenotypes for their association with QoL in patients. We then performed genome-wide association analyses of QoL and examined the association between polygenic risk scores (PRSs) for schizophrenia, major depressive disorder (MDD), and subjective wellbeing (SW) with QoL.\n\nResultsWe found nine phenotypes to be significantly and independently associated with QoL in patients, the most significant ones being negative (Beta=-1.17; SE=0.05, P=1x10-83; r2=53%), depressive (Beta=-1.07; SE=0.05; P=2x10-79; r2=51%) and emotional distress (Beta=-0.09; SE=0.01; P=4x10-59, r2=38%) symptoms. Schizophrenia and subjective wellbeing PRSs using various P-value thresholds were significantly and consistently associated with QoL (lowest association p-value = 6.8x10-6). Several sensitivity analyses confirmed the results.\n\nConclusionsVarious clinical phenotypes of schizophrenia as well as schizophrenia and subjective wellbeing polygenic risk scores are associated with QoL in schizophrenia patients and their relatives. These may be targeted by clinicians to more easily identify vulnerable schizophrenia patients for further social and clinical interventions to improve their QoL.