The influence of polygenic risk scores on the association between infections and schizophrenia
Several studies have suggested an important role of infections in the etiology of schizophrenia; however, shared genetic liability towards infections and schizophrenia could influence the association. We therefore investigated the possible effect of polygenic risk scores (PRS) for schizophrenia on the association between infections and the risk of schizophrenia utilizing the Danish registers combined with genetic information. We show that the PRS for schizophrenia and a history of infections have independent effects on the schizophrenia risk and that the PRS for schizophrenia did not influence the likelihood of getting an infection. While this study confirms the presence of a genetic risk for schizophrenia, we did not find evidence for a genetic liability to infections associated with the PRS. This does not necessarily imply that a genetic liability towards infections in people with schizophrenia is nonexistent but does suggest that it is distinct from the present PRS for schizophrenia.
About the study
Several studies have suggested an important role of infections in the etiology of schizophrenia; however, shared genetic liability towards infections and schizophrenia could influence the association. We therefore investigated the possible effect of polygenic risk scores (PRS) for schizophrenia on the association between infections and the risk of schizophrenia.
In order to investigate this we conducted a nested case-control study on a Danish population-based sample born after 1981 comprising of 1,692 cases diagnosed with schizophrenia between 1994-2008 and 1,724 matched controls identified in the Danish Neonatal Screening Biobank. All individuals were linked utilizing nationwide population-based registers with virtually complete registration of all hospital contacts for infections. PRS were calculated using discovery effect size estimates weights from an independent meta-analysis (34,600 cases and 45,968 control individuals).
Our results showed that a prior hospital contact with infection had occurred in 41% of the individuals with schizophrenia and increased the incidence rate ratio (IRR) of schizophrenia by 1.43 (95%CI=1.22-1.67). Adding PRS, which was robustly associated with schizophrenia (by an IRR of 1.46 (95%CI=1.34-1.60) per standard deviation of the score), did not alter the association with infections and the increased risk of schizophrenia remained (IRR=1.41; 95%CI=1.20-1.66). Furthermore, there were no interaction between PRS and infections on the risk of developing schizophrenia (p=0.554). Neither did PRS affect the risk of acquiring infections among patients with schizophrenia (OR=1.00; 95%CI=0.89-1.12) nor among controls (OR: 1.09; 95%CI: 0.96-1.24).
In conclusion, we show that infections were associated with an increased risk of schizophrenia that was not explained by the PRS for schizophrenia. Furthermore, the PRS for schizophrenia did not influence the likelihood of getting an infection both among individuals with schizophrenia and controls. While this study confirms the presence of a genetic risk for schizophrenia, we did not find evidence for a genetic liability to infections associated with the PRS. This does not necessarily imply that a genetic liability towards infections in people with schizophrenia is nonexistent but does suggest that it is distinct from the present PRS for schizophrenia.
The article “The influence of polygenic risk scores on the association between infections and schizophrenia” was published in Biological Psychiatry, April 2016 (In press).
Facts about the study
- Prior hospital contacts with infections had occurred in 41% of the individuals with schizophrenia
- PRS and a history of infections have independent effects on the schizophrenia risk and the common genetic risk measured by PRS did not account for the association with infection
- There were no interaction between PRS and infections on the risk of developing schizophrenia
- PRS did not affect the risk of acquiring infections among patients with schizophrenia or controls
Further information
Michael Eriksen Benrós, Senior Researcher, MD, PhD, Mental Health Centre Copenhagen, Copenhagen University Hospital