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The Capital Region of Denmark - a part of Copenhagen University Hospital
E-pub ahead of print

Schizophrenia polygenic risk scores, urbanicity and treatment-resistant schizophrenia

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  • Christiane Gasse
  • Theresa Wimberley
  • Yungpeng Wang
  • Ole Mors
  • Anders Børglum
  • Thomas Damm Als
  • Thomas Werge
  • Merete Nordentoft
  • David M Hougaard
  • Henriette Thisted Horsdal
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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.

Original languageEnglish
JournalSchizophrenia Research
Publication statusE-pub ahead of print - 22 Aug 2019

ID: 57958749