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

Published online by Cambridge University Press:  09 November 2011

C. B. Pedersen ,
D. Demontis ,
M. S. Pedersen ,
E. Agerbo ,
P. B. Mortensen ,
A. D. Børglum ,
D. M. Hougaard ,
M. V. Hollegaard ,
O. Mors  and
E. Cantor-Graae
C. B. Pedersen*
Affiliation:
National Centre for Register-based-Research, Aarhus University, Aarhus, Denmark
D. Demontis
Affiliation:
Department of Human Genetics, Aarhus University, Aarhus, Denmark
M. S. Pedersen
Affiliation:
National Centre for Register-based-Research, Aarhus University, Aarhus, Denmark
E. Agerbo
Affiliation:
National Centre for Register-based-Research, Aarhus University, Aarhus, Denmark
P. B. Mortensen
Affiliation:
National Centre for Register-based-Research, Aarhus University, Aarhus, Denmark
A. D. Børglum
Affiliation:
Department of Human Genetics, Aarhus University, Aarhus, Denmark Centre for Psychiatric Research, University Hospital, Risskov, Denmark
D. M. Hougaard
Affiliation:
Section of Neonatal Screening and Hormones, State Serum Institut, Copenhagen, Denmark
M. V. Hollegaard
Affiliation:
Section of Neonatal Screening and Hormones, State Serum Institut, Copenhagen, Denmark
O. Mors
Affiliation:
Centre for Psychiatric Research, University Hospital, Risskov, Denmark
E. Cantor-Graae
Affiliation:
Department of Clinical Sciences, Lund University, University Hospital Malmö, Malmö, Sweden
*
*Address for correspondence: Dr C. B. Pedersen, National Centre for Register-based Research, Aarhus University, Taasingegade 1, 8000 Aarhus C, Denmark. (Email: cbp@ncrr.dk)
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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.

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.

Keywords

Genome-wide associationimmigrantsprincipal componentschizophrenia
Type
Original Articles
Information
Psychological Medicine , Volume 42 , Issue 7 , July 2012 , pp. 1515 - 1521
Copyright
Copyright © Cambridge University Press 2011

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