1. Schizophrenia polygenic risk scores, urbanicity and treatment-resistant schizophrenia
- Author
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Thomas Damm Als, Ole Mors, Merete Nordentoft, David M. Hougaard, Henriette Thisted Horsdal, Anders D. Børglum, Thomas Werge, Christiane Gasse, Yungpeng Wang, and Theresa Wimberley
- Subjects
Adult ,Male ,Risk ,Multifactorial Inheritance ,Urban Population ,Denmark ,Geographical areas ,Treatment resistance ,Population-based ,Cohort Studies ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Medicine ,Genetic Predisposition to Disease ,Genetic liability ,Prospective Studies ,Treatment Failure ,Correlation of Data ,Biological Psychiatry ,business.industry ,Proportional hazards model ,Pharmacoepidemiology ,Hazard ratio ,Middle Aged ,medicine.disease ,Confidence interval ,030227 psychiatry ,Psychiatry and Mental health ,Schizophrenia ,Female ,Rural area ,business ,030217 neurology & neurosurgery ,Follow-Up Studies ,Demography ,Diagnosis of schizophrenia ,Cohort study - Abstract
INTRODUCTION: To investigate the impact of a polygenic risk score for schizophrenia (PRS-SZ) and urbanicity on the risk of treatment-resistant schizophrenia (TRS) in people diagnosed with schizophrenia and to evaluate the association between PRS-SZ and TRS across levels of urbanicity.METHODS: Cohort study of people born after 1981 with a first registered diagnosis of schizophrenia between 1996 and 2012 using Danish population registry data. Through linkage to genome-wide data, we calculated PRS-SZ based on a Psychiatric Genomics Consortium meta-analysis. We assessed urbanicity at birth (capital, provincial and rural areas). TRS was defined using prescription and hospital data. Performing Cox regression analysis, we calculated hazard rate ratios (HRs) and 95% confidence intervals (CI).RESULTS: Among 4475 people with schizophrenia, we identified 593 (13.3%) with TRS during 17,558 person years of follow-up. The adjusted HR for TRS associated with one standard deviation (SD) increase in the PRS-SZ was 1.11 (95% CI: 1.00-1.24). The adjusted HRs for TRS across levels of urbanicity were 1.20 (95% CI: 0.98-1.47) for provincial areas and 1.19 (95% CI 0.96-1.47) for rural areas compared with the capital area. Within strata of urbanicity, the adjusted HR for TRS was 1.39 (95% CI: 1.14-1.70) in the capital area with 1 SD increase in the PRS-SZ, 0.99 (95% CI 0.84-1.17) in provincial areas, and 1.03 (95% CI: 0.86-1.25) in rural areas.CONCLUSION: The effect of genetic liability (i.e. PRS) on risk of TRS varied across urbanicity levels and was highest for people with schizophrenia born in the capital areas.
- Published
- 2019