Association of The Polygenic Risk Score For Schizophrenia With Mortality And Suicidal Behaviour - A Danish Population-Based Study

Abstract

Background People who suffer from schizophrenia have a 15-20 year shorter life expectancy and are at increased risk of committing a suicide attempt. Adverse effects of family histories of mental disorders, sedentary lifestyles, side effects of medical treatments, and insufficient somatic treatments are contributing factors. However, it is unknown whether an increased genetic liability to schizophrenia influences the risk of dying early and commenting a suicide attempt. Our objectives was to determine whether the genetic predisposition to schizophrenia is associated with the risk of dying early and experience a suicide attempt. Methods Design and Settings: Case control study. Setting: Denmark. Participants: Cases diagnosed with schizophrenia in the period 1994-2008 who were born after 1982(n=1780) and 1768 matched population-based controls. Exposure: The polygenic risk score for schizophrenia Main Outcomes and Measures: The outcome of interest was death and suicide attempts in cases and controls. 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). Results 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. Discussion A genetic predisposition for schizophrenia, measured by PRS, has little influence on the excess mortality or the high risk of suicide attempts. In contrast there is a strong significant effect of family history of mental disorders. Therefore, the excess mortality may more likely be attributable to modifiable factors connected to growing up or living in a family with mental disorders, and more general modifiable risk factors such as inadequate somatic treatment and sedentary life lifestyles. However, our sample was only of limited size