title: Genetic liability for schizophrenia predicts risk of immune disorders.
abstract: BACKGROUND
  Schizophrenia patients and their parents have an increased risk of immune disorders compared to population controls and their parents. This may be explained by genetic overlap in the pathogenesis of both types of disorders. The purpose of this study was to investigate the genetic overlap between schizophrenia and three immune disorders and to compare with the overlap between schizophrenia and two disorders not primarily characterized by immune dysregulation: bipolar disorder and type 2 diabetes.
  
  
  METHODS
  We performed a polygenic risk score analysis using results from the schizophrenia Psychiatric GWAS consortium (PGC) (8922 cases and 9528 controls) and five Wellcome Trust Case Control Consortium (WTCCC) case samples as target cases: bipolar disorder (n=1998), type 1 diabetes (n=2000), Crohn's diseases (n=2005), rheumatoid arthritis (n=1999), and type 2 diabetes (n=1999). The WTCCC British Birth Cohort and National Blood Service samples (n=3004) were used as target controls. Additionally, we tested whether schizophrenia polygenic risk scores significantly differed between patients with immune disorder, bipolar disorder, and type 2 diabetes respectively.
  
  
  RESULTS
  Polygenic risk scores for schizophrenia significantly predicted disease status in all three immune disorder samples (Nagelkerke-R(2) 1.1%-1.3%; p<0.05). The polygenic risk of schizophrenia in patients with immune disorders was significantly lower than in patients with bipolar disorder (Nagelkerke-R(2) 6.0%; p<0.05), but higher than in type 2 diabetes patients (Nagelkerke-R(2) 0.5%; p<0.05).
  
  
  CONCLUSIONS
  Our results suggest that genetic factors are shared between schizophrenia and immune disorders. This contributes to an accumulating body of evidence that immune processes may play a role in the etiology of schizophrenia.
authors.affiliation: Department of Psychiatry, Amsterdam Medical Center, Amsterdam, The Netherlands; Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center, Utrecht, The Netherlands.
authors.forename: Sven
authors.initials: S
authors.lastname: Stringer
authors.affiliation: Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center, Utrecht, The Netherlands.
authors.forename: René S
authors.initials: RS
authors.lastname: Kahn
authors.affiliation: Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center, Utrecht, The Netherlands.
authors.forename: Lot D
authors.initials: LD
authors.lastname: de Witte
authors.affiliation: Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center, Utrecht, The Netherlands; University California Los Angeles, Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA, USA.
authors.forename: Roel A
authors.initials: RA
authors.lastname: Ophoff
authors.affiliation: Department of Psychiatry, Amsterdam Medical Center, Amsterdam, The Netherlands.
authors.forename: Eske M
authors.initials: EM
authors.lastname: Derks
mesh_terms: D016022:Case-Control Studies; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007154:Immune System Diseases / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011237:Predictive Value of Tests; D025341:Principal Component Analysis; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology* / Q000235:genetics*
keywords: Genetic overlap; Genome-wide association study; Human leukocyte antigen system; Immune dysregulation; Major histocompatibility complex; Polygenic risk score