Schizophrenia polygenic risk scores, urbanicity and treatment-resistant schizophrenia

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  • Christiane Gasse
  • Theresa Wimberley
  • Yungpeng Wang, 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.
  • ,
  • Ole Mors
  • Anders Børglum
  • Thomas Damm Als
  • Thomas Werge, Institute of Biological Psychiatry, MHC Sct. Hans, Mental Health Services Copenhagen, Roskilde 4000, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen 2200, Denmark.
  • ,
  • Merete Nordentoft, Copenhagen University Hospital, Mental Health Centre Copenhagen, Mental Health Services, Capital Region of Denmark, and the Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark; Center for Child and Adolescent Psychiatry Capital Region, Copenhagen.
  • ,
  • David M Hougaard, iPSYCH - The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark; Danish Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institute, Denmark.
  • ,
  • Henriette Thisted Horsdal

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
Volume212
Pages (from-to)79-85
Number of pages7
ISSN0920-9964
DOIs
Publication statusPublished - Oct 2019

    Research areas

  • Genetic liability, Geographical areas, Pharmacoepidemiology, Population-based, Schizophrenia, Treatment resistance

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