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Schizophr Res. 2019 Oct;212:79-85. doi: 10.1016/j.schres.2019.08.008. Epub 2019 Aug 22.

Schizophrenia polygenic risk scores, urbanicity and treatment-resistant schizophrenia.

Author information

1
NCRR - National Centre for Register-based Research, Aarhus University, Aarhus, Denmark; iPSYCH - The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark; CIRRAU - Centre for Integrated Register-Based Research at Aarhus University, Aarhus, Denmark; Department for Depression and Anxiety, Aarhus University Hospital - Psychiatry, Aarhus, Denmark. Electronic address: chgass@rm.dk.
2
NCRR - National Centre for Register-based Research, Aarhus University, Aarhus, Denmark.
3
iPSYCH - The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark; NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Department of Neurosciences, University of California, San Diego, La Jolla, CA, United States of America; Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, CA, United States of America.
4
iPSYCH - The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark; Psychosis Research Unit, Aarhus University Hospital - Psychiatry, Aarhus, Denmark.
5
iPSYCH - The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark; Department of Biomedicine and Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark; Center for Genomics and Personalized Medicine, Central Region Denmark and Aarhus University, Aarhus, Denmark.
6
iPSYCH - The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark; Institute of Biological Psychiatry, MHC Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
7
iPSYCH - The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark; Copenhagen University Hospital, Mental Health Center Copenhagen, Mental Health Services in the Capital Region of Denmark, Denmark.
8
iPSYCH - The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark; Danish Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institute, Denmark.
9
NCRR - National Centre for Register-based Research, Aarhus University, Aarhus, Denmark; iPSYCH - The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark.

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.

KEYWORDS:

Genetic liability; Geographical areas; Pharmacoepidemiology; Population-based; Schizophrenia; Treatment resistance

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