title: Risk of schizophrenia in relation to parental origin and genome-wide divergence.
abstract: BACKGROUND
  Second-generation immigrants have an increased risk of schizophrenia, a finding that still lacks a satisfactory explanation. Various operational definitions of second-generation immigrants have been used, including foreign parental country of birth. However, with increasing global migration, it is not clear that parental country of birth necessarily is informative with regard to ethnicity. We compare two independently collected measures of parental foreign ethnicity, parental foreign country of birth versus genetic divergence, based on genome-wide genotypic data, to access which measure most efficiently captures the increased risk of schizophrenia among second-generation immigrants residing in Denmark.
  
  
  METHODS
  A case-control study covering all children born in Denmark since 1981 included 892 cases of schizophrenia and 883 matched controls. Genetic divergence was assessed using principal component analyses of the genotypic data. Independently, parental foreign country of birth was assessed using information recorded prospectively in the Danish Civil Registration System. We compared incidence rate ratios of schizophrenia associated with these two independently collected measures of parental foreign ethnicity.
  
  
  RESULTS
  People with foreign-born parents had a significantly increased risk of schizophrenia [relative risk (RR) 1.94 (95% confidence intervals (CI) 1.41-2.65)]. Genetically divergent persons also had a significant increased risk [RR 2.43 (95% CI 1.55-3.82)]. Mutual adjustment of parental foreign country of birth and genetic divergence showed no difference between these measures with regard to their potential impact on the results.
  
  
  CONCLUSIONS
  In terms of RR of schizophrenia, genetic divergence and parental foreign country of birth are interchangeable entities, and both entities have validity with regard to identifying second-generation immigrants.
authors: National Centre for Register-based-Research, Aarhus University, Aarhus, Denmark. cbp@ncrr.dk
authors: C B
authors: CB
authors: Pedersen
authors: D
authors: D
authors: Demontis
authors: M S
authors: MS
authors: Pedersen
authors: E
authors: E
authors: Agerbo
authors: P B
authors: PB
authors: Mortensen
authors: A D
authors: AD
authors: Børglum
authors: D M
authors: DM
authors: Hougaard
authors: M V
authors: MV
authors: Hollegaard
authors: O
authors: O
authors: Mors
authors: E
authors: E
authors: Cantor-Graae
mesh_terms: D016022:Case-Control Studies; D002648:Child; D003718:Denmark / Q000453:epidemiology; D054242:Emigrants and Immigrants / Q000523:psychology / Q000706:statistics & numerical data*; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D010290:Parents; D025341:Principal Component Analysis; D012042:Registries; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics