title: Influence of Polygenic Risk Scores on the Association Between Infections and Schizophrenia.
abstract: Several studies have suggested an important role of infections in the etiology of schizophrenia; however, shared genetic liability toward infections and schizophrenia could influence the association. We therefore investigated the possible effect of polygenic risk scores (PRSs) for schizophrenia on the association between infections and the risk of schizophrenia.
  
  
  
  We conducted a nested case-control study on a Danish population-based sample born after 1981 comprising of 1692 cases diagnosed with schizophrenia between 1994 and 2008 and 1724 matched controls. All individuals were linked utilizing nationwide population-based registers with virtually complete registration of all hospital contacts for infections. PRSs were calculated using discovery effect size estimates weights from an independent meta-analysis (34,600 cases and 45,968 control individuals).
  
  
  
  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% confidence interval [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 interactions between PRS and infections on the risk of developing schizophrenia (p = .554). Neither did PRS affect the risk of acquiring infections among patients with schizophrenia (odds ratio = 1.00; 95% CI = 0.89-1.12) nor among controls (odds ratio = 1.09; 95% CI: 0.96-1.24).
  
  
  
  PRS and a history of infections have independent effects on the risk for schizophrenia, and the common genetic risk measured by PRS did not account for the association with infection in this sample.
authors.affiliation: Mental Health Centre Copenhagen, University of Copenhagen, Faculty of Health Sciences, Copenhagen; National Centre for Register-Based Research, Aarhus University, Aarhus; The Lundbeck Foundation Initiative for Integrative Psychiatric Research iPSYCH, Copenhagen. Electronic address: Benros@dadlnet.dk.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Benros
authors.affiliation: National Centre for Register-Based Research, Aarhus University, Aarhus; The Lundbeck Foundation Initiative for Integrative Psychiatric Research iPSYCH, Copenhagen.
authors.forename: Betina B
authors.initials: BB
authors.lastname: Trabjerg
authors.affiliation: National Centre for Register-Based Research, Aarhus University, Aarhus; The Lundbeck Foundation Initiative for Integrative Psychiatric Research iPSYCH, Copenhagen.
authors.forename: Sandra
authors.initials: S
authors.lastname: Meier
authors.affiliation: The Lundbeck Foundation Initiative for Integrative Psychiatric Research iPSYCH, Copenhagen; Department of Biomedicine and Centre for Integrative Sequencing (iSEQ), Aarhus University, Aarhus.
authors.forename: Manuel
authors.initials: M
authors.lastname: Mattheisen
authors.affiliation: National Centre for Register-Based Research, Aarhus University, Aarhus; The Lundbeck Foundation Initiative for Integrative Psychiatric Research iPSYCH, Copenhagen.
authors.forename: Preben B
authors.initials: PB
authors.lastname: Mortensen
authors.affiliation: The Lundbeck Foundation Initiative for Integrative Psychiatric Research iPSYCH, Copenhagen; Research Department P, Aarhus University Hospital, Risskov.
authors.forename: Ole
authors.initials: O
authors.lastname: Mors
authors.affiliation: The Lundbeck Foundation Initiative for Integrative Psychiatric Research iPSYCH, Copenhagen; Department of Biomedicine and Centre for Integrative Sequencing (iSEQ), Aarhus University, Aarhus.
authors.forename: Anders D
authors.initials: AD
authors.lastname: Børglum
authors.affiliation: Danish Centre for Neonatal Screening, Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: David M
authors.initials: DM
authors.lastname: Hougaard
authors.affiliation: Danish Centre for Neonatal Screening, Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Bent
authors.initials: B
authors.lastname: Nørgaard-Pedersen
authors.affiliation: The Lundbeck Foundation Initiative for Integrative Psychiatric Research iPSYCH, Copenhagen.
authors.forename: Merete
authors.initials: M
authors.lastname: Nordentoft
authors.affiliation: National Centre for Register-Based Research, Aarhus University, Aarhus; The Lundbeck Foundation Initiative for Integrative Psychiatric Research iPSYCH, Copenhagen; CIRRAU-Centre for Integrated Register-Based Research, Aarhus University, Aarhus.
authors.forename: Esben
authors.initials: E
authors.lastname: Agerbo
mesh_terms: D016022:Case-Control Studies; D003718:Denmark / Q000453:epidemiology; D005192:Family Health / Q000706:statistics & numerical data; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D007239:Infections / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D020412:Multifactorial Inheritance / Q000235:genetics*; D012042:Registries; D012307:Risk Factors; D012559:Schizophrenia / Q000150:complications / Q000453:epidemiology / Q000235:genetics*
keywords: Epidemiology; Genetics; Infections; Polygenic risk score; Register-based; Schizophrenia