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Genetic Overlap Between Schizophrenia and Developmental Psychopathology: Longitudinal and Multivariate Polygenic Risk Prediction of Common Psychiatric Traits During Development

Research output: Contribution to journalArticle

Original languageEnglish
Article numbersbx031
Pages (from-to)1197-1207
Number of pages11
JournalSchizophrenia Bulletin
Volume43
Issue number6
Early online date11 Mar 2017
DOIs
DateAccepted/In press - 3 Feb 2017
DateE-pub ahead of print - 11 Mar 2017
DatePublished (current) - Nov 2017

Abstract

BACKGROUND: Several nonpsychotic psychiatric disorders in childhood and adolescence can precede the onset of schizophrenia, but the etiology of this relationship remains unclear. We investigated to what extent the association between schizophrenia and psychiatric disorders in childhood is explained by correlated genetic risk factors.

METHODS: Polygenic risk scores (PRS), reflecting an individual's genetic risk for schizophrenia, were constructed for 2588 children from the Netherlands Twin Register (NTR) and 6127 from the Avon Longitudinal Study of Parents And Children (ALSPAC). The associations between schizophrenia PRS and measures of anxiety, depression, attention deficit hyperactivity disorder (ADHD), and oppositional defiant disorder/conduct disorder (ODD/CD) were estimated at age 7, 10, 12/13, and 15 years in the 2 cohorts. Results were then meta-analyzed, and a meta-regression analysis was performed to test differences in effects sizes over, age and disorders.

RESULTS: Schizophrenia PRS were associated with childhood and adolescent psychopathology. Meta-regression analysis showed differences in the associations over disorders, with the strongest association with childhood and adolescent depression and a weaker association for ODD/CD at age 7. The associations increased with age and this increase was steepest for ADHD and ODD/CD. Genetic correlations varied between 0.10 and 0.25.

CONCLUSION: By optimally using longitudinal data across diagnoses in a multivariate meta-analysis this study sheds light on the development of childhood disorders into severe adult psychiatric disorders. The results are consistent with a common genetic etiology of schizophrenia and developmental psychopathology as well as with a stronger shared genetic etiology between schizophrenia and adolescent onset psychopathology.

    Structured keywords

  • Brain and Behaviour
  • Tobacco and Alcohol

    Research areas

  • Developmental psychiatry, Schizophrenia prodrome, Genetic epidemiology

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  • Full-text PDF (accepted author manuscript)

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Oxford University Press at https://academic.oup.com/schizophreniabulletin/article/3065926/Genetic. Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 220 KB, Word document

  • Table 1

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Oxford University Press at https://academic.oup.com/schizophreniabulletin/article/3065926/Genetic. Please refer to any applicable terms of use of the publisher.

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  • Table 2

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Oxford University Press at https://academic.oup.com/schizophreniabulletin/article/3065926/Genetic. Please refer to any applicable terms of use of the publisher.

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  • Figure 1

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Oxford University Press at https://academic.oup.com/schizophreniabulletin/article/3065926/Genetic. Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 1 MB, image/tiff

  • Figure 2

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Oxford University Press at https://academic.oup.com/schizophreniabulletin/article/3065926/Genetic. Please refer to any applicable terms of use of the publisher.

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    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Oxford University Press at https://academic.oup.com/schizophreniabulletin/article/3065926/Genetic. Please refer to any applicable terms of use of the publisher.

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  • Supplementary information PDF

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Oxford University Press at https://academic.oup.com/schizophreniabulletin/article/3065926/Genetic. Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 319 KB, PDF document

  • Supplementary information XLS Table S1

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Oxford University Press at https://academic.oup.com/schizophreniabulletin/article/3065926/Genetic. Please refer to any applicable terms of use of the publisher.

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  • Supplementary information XLS Table S2

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Oxford University Press at https://academic.oup.com/schizophreniabulletin/article/3065926/Genetic. Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 20 KB, application/vndms-excel

  • Supplementary information XLS Table S3

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Oxford University Press at https://academic.oup.com/schizophreniabulletin/article/3065926/Genetic. Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 17 KB, application/vndms-excel

  • Supplementary information XLS Table S4

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Oxford University Press at https://academic.oup.com/schizophreniabulletin/article/3065926/Genetic. Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 21 KB, application/vndms-excel

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