Psychological Medicine

Original Articles

Risk of schizophrenia in relation to parental origin and genome-wide divergence

C. B. Pedersena1 c1, D. Demontisa2, M. S. Pedersena1, E. Agerboa1, P. B. Mortensena1, A. D. Børgluma2a4, D. M. Hougaarda3, M. V. Hollegaarda3, O. Morsa4 and E. Cantor-Graaea5

a1 National Centre for Register-based-Research, Aarhus University, Aarhus, Denmark

a2 Department of Human Genetics, Aarhus University, Aarhus, Denmark

a3 Section of Neonatal Screening and Hormones, State Serum Institut, Copenhagen, Denmark

a4 Centre for Psychiatric Research, University Hospital, Risskov, Denmark

a5 Department of Clinical Sciences, Lund University, University Hospital Malmö, Malmö, Sweden


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.

Method 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.

(Received June 07 2011)

(Revised September 22 2011)

(Accepted September 26 2011)

(Online publication November 09 2011)


c1 Address for correspondence: Dr C. B. Pedersen, National Centre for Register-based Research, Aarhus University, Taasingegade 1, 8000 Aarhus C, Denmark. (Email: