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The role of genetic liability in the association of urbanicity at birth and during upbringing with schizophrenia in Denmark

Published online by Cambridge University Press:  29 June 2017

D. Paksarian ,
B. B. Trabjerg ,
K. R. Merikangas ,
O. Mors ,
A. D. Børglum ,
D. M. Hougaard ,
J. J. McGrath ,
C. B. Pedersen ,
P. B. Mortensen  and
E. Agerbo
D. Paksarian*
Affiliation:
Genetic Epidemiology Research Branch, National Institute of Mental Health, Bethesda, MD, USA
B. B. Trabjerg
Affiliation:
NCRR-National Center for Register-Based Research, Business and Social Sciences, Aarhus University, Aarhus, Denmark The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark CIRRAU–Centre for Integrated Register-Based Research, Aarhus University, Aarhus, Denmark
K. R. Merikangas
Affiliation:
Genetic Epidemiology Research Branch, National Institute of Mental Health, Bethesda, MD, USA
O. Mors
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark Department P, Aarhus University Hospital, Risskov, Denmark
A. D. Børglum
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark Department P, Aarhus University Hospital, Risskov, Denmark Department of Biomedicine and Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark
D. M. Hougaard
Affiliation:
Danish Center for Neonatal Screening, Statens Serum Institut, Copenhagen, Denmark
J. J. McGrath
Affiliation:
NCRR-National Center for Register-Based Research, Business and Social Sciences, Aarhus University, Aarhus, Denmark Queensland Brain Institute, The University of Queensland, St Lucia, Australia
C. B. Pedersen
Affiliation:
NCRR-National Center for Register-Based Research, Business and Social Sciences, Aarhus University, Aarhus, Denmark The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark CIRRAU–Centre for Integrated Register-Based Research, Aarhus University, Aarhus, Denmark
P. B. Mortensen
Affiliation:
NCRR-National Center for Register-Based Research, Business and Social Sciences, Aarhus University, Aarhus, Denmark The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark CIRRAU–Centre for Integrated Register-Based Research, Aarhus University, Aarhus, Denmark
E. Agerbo
Affiliation:
NCRR-National Center for Register-Based Research, Business and Social Sciences, Aarhus University, Aarhus, Denmark The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark CIRRAU–Centre for Integrated Register-Based Research, Aarhus University, Aarhus, Denmark
*
*Address for correspondence: D. Paksarian, Genetic Epidemiology Research Branch, National Institute of Mental Health, 35A Convent Drive, MSC#3720, Bethesda, MD 20892, USA. (Email: diana.paksarian@nih.gov)
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Abstract

Background

Studies have indicated that the association of urbanicity at birth and during upbringing with schizophrenia may be driven by familial factors such as genetic liability. We used a population-based nested case–control study to assess whether polygenic risk score (PRS) for schizophrenia was associated with urbanicity at birth and at age 15, and to assess whether PRS and parental history of mental disorder together explained the association between urbanicity and schizophrenia.

Methods

Data were drawn from Danish population registries. Cases born since 1981 and diagnosed with schizophrenia between 1994 and 2009 were matched to controls with the same sex and birthdate (1549 pairs). Genome-wide data were obtained from the Danish Neonatal Screening Biobank and PRSs were calculated based on results of a separate, large meta-analysis.

Results

Those with higher PRS were more likely reside in the capital compared with rural areas at age 15 [odds ratio (OR) 1.19, 95% confidence interval (CI) 1.01–1.40], but not at birth (OR 1.09, 95% CI 0.95–1.26). Adjustment for PRS produced almost no change in relative risks of schizophrenia associated with urbanicity at birth, but slightly attenuated those for urban residence at age 15. Additional adjustment for parental history led to slight attenuation of relative risks for urbanicity at birth [incidence rate ratio (IRR) for birth in capital = 1.54, 95% CI 1.18–2.02; overall p = 0.016] and further attenuation of relative risks for urbanicity at age 15 (IRR for residence in capital = 1.32, 95% CI 0.97–1.78; overall p = 0.148).

Conclusions

While results regarding urbanicity during upbringing were somewhat equivocal, genetic liability as measured here does not appear to explain the association between urbanicity at birth and schizophrenia.

Keywords

Epidemiologypolygenic risk scoreschizophreniaurbanicityselective migration
Type
Original Articles
Information
Psychological Medicine , Volume 48 , Issue 2 , January 2018 , pp. 305 - 314
Copyright
Copyright © Cambridge University Press 2017 

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