Phenome-wide and genome-wide analyses of quality of life in schizophrenia

Copyright © The Author(s), 2020. Background: Schizophrenia negatively affects quality of life (QoL). A handful of variables from small studies have been reported to influence QoL in patients with schizophrenia, but a study comprehensively dissecting the genetic and non-genetic contributing factors to QoL in these patients is currently lacking. Aims: We adopted a hypothesis-generating approach to assess the phenotypic and genotypic determinants of QoL in schizophrenia. Method: The study population comprised 1119 patients with a psychotic disorder, 1979 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 for schizophrenia, major depressive disorder and subjective well-being and QoL. Results: We found nine phenotypes to be significantly and independently associated with QoL in patients, the most significant ones being negative (β = −1.17; s.e. 0.05; P = 1 × 10–83; r2 = 38%), depressive (β = −1.07; s.e. 0.05; P = 2 × 10–79; r2 = 36%) and emotional distress (β = −0.09; s.e. 0.01; P = 4 × 10–59, r2 = 25%) symptoms. Schizophrenia and subjective well-being polygenic risk scores, using various P-value thresholds, were significantly and consistently associated with QoL (lowest association P-value = 6.8 × 10–6). Several sensitivity analyses confirmed the results. Conclusions: Various clinical phenotypes of schizophrenia, as well as schizophrenia and subjective well-being polygenic risk scores, are associated with QoL in patients with schizophrenia and their relatives. These may be targeted by clinicians to more easily identify vulnerable patients with schizophrenia for further social and clinical interventions to improve their QoL. Dutch Health Research Council; Lundbeck; AstraZeneca; Eli Lilly; Janssen Cilag;Amsterdam: Academic Psychiatric Centre of the Academic Medical Center and the mental health institutions at Geestelijke Gezondheidszorg (GGZ) Ingeest; Arkin; Dijk en Duin; GGZ Rivierduinen; Erasmus Medical Centre and GGZ Noord Holland Noord; Groningen: University Medical Center Groningen and the mental health institutions at Lentis; GGZ Friesland; GGZ Drenthe; Dimence; Mediant; GGNet Warnsveld; Yulius Dordrecht and Parnassia Psycho-Medical Center The Hague; Maastricht: Maastricht University Medical Centre and the mental health institutions at GGZ Eindhoven en De Kempen; GGZ Breburg; GGZ Oost-Brabant; Vincent van Gogh voor Geestelijke Gezondheid; Mondriaan; Virenze riagg; Zuyderland GGZ; MET ggz; Universitair Centrum Sint-Jozef Kortenberg; Collaborative Antwerp Psychiatric Research Institute University of Antwerp; Psychiatrisch Centrum Ziekeren Sint-Truiden; Psychiatrisch Ziekenhuis Sancta Maria Sint-Truiden; GGZ Overpelt and Openbaar Psychiatrisch Zorgcentrum Rekem; Utrecht: University Medical Center Utrecht and the mental health institutions Altrecht; GGZ Centraal and Delta