title: Association of the polygenic risk score for schizophrenia with mortality and suicidal behavior - A Danish population-based study.
abstract: It is unknown whether an increased genetic liability to schizophrenia influences the risk of dying early. The aim of the study was to determine whether the genetic predisposition to schizophrenia is associated with the risk of dying early and experience a suicide attempt.
  
  
  
  Case control study, Denmark. The main measure was the mortality rate ratios (MRR) for deaths and odds ratios (OR) for multiple suicide attempts, associated with one standard deviations increase of the polygenic risk-score for schizophrenia (PRS).
  
  
  
  We replicated the high mortality MRR=9.01 (95% CI: 3.56-22.80), and high risk of multiple suicide attempts OR=33.16 (95% CI: 20.97-52.43) associated with schizophrenia compared to the general population. However, there was no effect of the PRS on mortality MRR=1.00 (95% CI 0.71-1.40) in the case-control setup or in cases only, MRR=1.05 (95% CI 0.73-1.51). Similar, no association between the PRS and multiple suicide attempts was found in the adjusted models, but in contrast, family history of mental disorders was associated with both outcomes.
  
  
  
  A genetic predisposition for schizophrenia, measured by PRS, has little influence on the excess mortality or the risk of suicide attempts. In contrast there is a strong significant effect of family history of mental disorders. Our findings could reflect that the common variants detected by recent PRS only explain a small proportion of risk of schizophrenia, and that future, more powerful PRS instruments may be able to predict excess mortality within this disorder.
authors.affiliation: Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; National Centre for Register-Based Research, Aarhus University, Denmark; Mental Health in Primary Care (MEPRICA), Research Unit for General Practice, Department of Public Health, Aarhus University, Aarhus, Denmark. Electronic address: tml@econ.au.dk.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Laursen
authors.affiliation: Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; National Centre for Register-Based Research, Aarhus University, Denmark.
authors.forename: Betina B
authors.initials: BB
authors.lastname: Trabjerg
authors.affiliation: Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Mors
authors.affiliation: Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark; Department of Biomedicine and Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.
authors.forename: Anders D
authors.initials: AD
authors.lastname: Børglum
authors.affiliation: Danish Center for Neonatal Screening, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: David M
authors.initials: DM
authors.lastname: Hougaard
authors.affiliation: Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark.
authors.forename: Manuel
authors.initials: M
authors.lastname: Mattheisen
authors.affiliation: Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; National Centre for Register-Based Research, Aarhus University, Denmark.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Meier
authors.affiliation: The University of Queensland, Queensland Brain Institute, Brisbane, Australia.
authors.forename: Enda M
authors.initials: EM
authors.lastname: Byrne
authors.affiliation: Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; National Centre for Register-Based Research, Aarhus University, Denmark.
authors.forename: Preben B
authors.initials: PB
authors.lastname: Mortensen
authors.affiliation: Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; National Centre for Register-Based Research, Aarhus University, Denmark.
authors.forename: Trine
authors.initials: T
authors.lastname: Munk-Olsen
authors.affiliation: Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; National Centre for Register-Based Research, Aarhus University, Denmark; CIRRAU - Centre for Integrated Register-based Research at Aarhus University, Aarhus, Denmark.
authors.forename: Esben
authors.initials: E
authors.lastname: Agerbo
mesh_terms: D000293:Adolescent; D000328:Adult; D018070:Biological Specimen Banks; D016022:Case-Control Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D061213:Mortality, Premature; D020412:Multifactorial Inheritance; D012042:Registries; D012306:Risk; D012559:Schizophrenia / Q000235:genetics* / Q000401:mortality*; D013406:Suicide, Attempted / Q000706:statistics & numerical data*; D055815:Young Adult
keywords: Epidemiology; Mortailty; Polygenic risk score; Schizophrenia