Schizophrenia polygenic risk scores, urbanicity and treatment-resistant schizophrenia

SCHIZOPHRENIA RESEARCH

卷:212

Article

Gasse, Christiane^1,2,3,4  Wimberley, Theresa¹  Wang, Yungpeng^2,5,6,7,8  Mors, Ole^2,9  Borglum, Anders^{2,10,11,12,13}  Als, Thomas Damm^{2,10,11,12,13}  Werge, Thomas^2,14,15  Nordentoft, Merete^2,16  Hougaard, David M.^2,17  Horsdal, Henriette Thisted^1,2 

[1] Aarhus Univ, NCRR Natl Ctr Register Based Res, Aarhus, Denmark

[2] iPSYCH Lundbeck Fdn Initiat Integrat Psychiat Res, Aarhus, Denmark

[3] Aarhus Univ, CIRRAU Ctr Integrated Register Based Res, Aarhus, Denmark

[4] Aarhus Univ Hosp Psychiat, Dept Depress & Anxiety, Aarhus, Denmark

[5] Univ Oslo, KG Jebsen Ctr Psychosis Res, Inst Clin Med, NORMENT, Oslo, Norway

[6] Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway

[7] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA

[8] Univ Calif San Diego, Multimodal Imaging Lab, La Jolla, CA 92093 USA

[9] Aarhus Univ Hosp Psychiat, Psychosis Res Unit, Aarhus, Denmark

[10] Aarhus Univ, Dept Biomed, Aarhus, Denmark

[11] Aarhus Univ, Ctr Integrat Sequencing, iSEQ, Aarhus, Denmark

[12] Cent Reg Denmark, Ctr Genom & Personalized Med, Aarhus, Denmark

[13] Aarhus Univ, Aarhus, Denmark

[14] Mental Hlth Serv Copenhagen, Inst Biol Psychiat, MHC Sct Hans, Roskilde, Denmark

[15] Univ Copenhagen, Dept Clin Med, Copenhagen, Denmark

[16] Copenhagen Univ Hosp, Mental Hlth Ctr Copenhagen, Mental Hlth Serv Capital Reg Denmark, Copenhagen, Denmark

[17] Statens Serum Inst, Danish Ctr Neonatal Screening, Dept Congenital Disorders, Copenhagen, Denmark

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

DOI  :  10.1016/j.schres.2019.08.008

来源: Elsevier

【 摘 要 】

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. (C) 2019 Elsevier B.V. All rights reserved.

【 授权许可】

Free