TY - JOUR
T1 - Schizophrenia polygenic risk scores, urbanicity and treatment-resistant schizophrenia
AU - Gasse, Christiane
AU - Wimberley, Theresa
AU - Wang, Yungpeng
AU - Mors, Ole
AU - Børglum, Anders
AU - Als, Thomas Damm
AU - Werge, Thomas
AU - Nordentoft, Merete
AU - Hougaard, David M.
AU - Horsdal, Henriette Thisted
PY - 2019/10
Y1 - 2019/10
N2 - 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.
AB - 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.
KW - Genetic liability
KW - Pharmacoepidemiology
KW - Population-based
KW - Schizophrenia
KW - Treatment resistance
KW - Geographical areas
U2 - 10.1016/j.schres.2019.08.008
DO - 10.1016/j.schres.2019.08.008
M3 - Journal article
C2 - 31447354
SN - 0920-9964
VL - 212
SP - 79
EP - 85
JO - Schizophrenia Research
JF - Schizophrenia Research
ER -