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. 2018 Jan;48(2):305-314.
doi: 10.1017/S0033291717001696. Epub 2017 Jun 29.

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

D Paksarian  1 , B B Trabjerg  2 , K R Merikangas  1 , O Mors  3 , A D Børglum  3 , D M Hougaard  4 , J J McGrath  2 , C B Pedersen  2 , P B Mortensen  2 , E Agerbo  2
Affiliations

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

D Paksarian et al. Psychol Med. 2018 Jan.

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: Epidemiology; polygenic risk score; schizophrenia; selective migration; urbanicity.

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Conflict of interest statement

Conflict of Interest: None.

Figures

Figure 1:
Figure 1:
Mean polygenic risk score for schizophrenia, according to urbanicity at birth and at age 15, among 3,416 schizophrenia cases and controls. Polygenic risk score adjusted for the first 10 principal components as well as age, sex, and year of birth. Only those whose date of matching (case onset) is after the 15th birthday and who lived in Denmark at age 15 (n=3,214) are used when considering urbanicity at age 15.
See this image and copyright information in PMC

References

    1. AGERBO E, MORTENSEN PB, WIUF C, PEDERSEN MS, MCGRATH J, HOLLEGAARD MV, NORGAARD-PEDERSEN B, HOUGAARD DM, MORS O & PEDERSEN CB 2012. Modelling the contribution of family history and variation in single nucleotide polymorphisms to risk of schizophrenia: a Danish national birth cohort-based study. Schizophr Res, 134, 246–52. - PubMed
    1. AGERBO E, SULLIVAN PF, VILHJALMSSON BJ, PEDERSEN CB, MORS O, BORGLUM AD, HOUGAARD DM, HOLLEGAARD MV, MEIER S, MATTHEISEN M, RIPKE S, WRAY NR & MORTENSEN PB 2015. Polygenic Risk Score, Parental Socioeconomic Status, Family History of Psychiatric Disorders, and the Risk for Schizophrenia: A Danish Population-Based Study and Meta-analysis. JAMA Psychiatry, 72, 635–41. - PubMed
    1. BENROS ME, TRABJERG BB, MEIER S, MATTHEISEN M, MORTENSEN PB, MORS O, BORGLUM AD, HOUGAARD DM, NORGAARD-PEDERSEN B, NORDENTOFT M & AGERBO E 2016. Influence of Polygenic Risk Scores on the Association Between Infections and Schizophrenia. Biol Psychiatry. - PubMed
    1. BORGLUM AD, DEMONTIS D, GROVE J, PALLESEN J, HOLLEGAARD MV, PEDERSEN CB, HEDEMAND A, MATTHEISEN M, INVESTIGATORS G, UITTERLINDEN A, NYEGAARD M, ORNTOFT T, WIUF C, DIDRIKSEN M, NORDENTOFT M, NOTHEN MM, RIETSCHEL M, OPHOFF RA, CICHON S, YOLKEN RH, HOUGAARD DM, MORTENSEN PB & MORS O 2014. Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci. Mol Psychiatry, 19, 325–33. - PMC - PubMed
    1. CANTOR-GRAAE E & PEDERSEN CB 2007. Risk of schizophrenia in second-generation immigrants: a Danish population-based cohort study. Psychological Medicine, 37, 485–494. - PubMed