Journal
SCHIZOPHRENIA BULLETIN
Volume 43, Issue 6, Pages 1197-1207Publisher
OXFORD UNIV PRESS
DOI: 10.1093/schbul/sbx031
Keywords
developmental psychiatry; schizophrenia prodrome; genetic epidemiology
Categories
Funding
- UK Medical Research Council
- Wellcome Trust [102215/2/13/2]
- University of Bristol
- Medical Research Council Integrative Epidemiology Unit at the University of Bristol [MC_UU_12013/6]
- Genetic influences on stability and change in psychopathology from childhood to young adulthood, Netherlands Organization for Scientific Research (NWO) [ZonMW 912-10-020]
- Genetics of Mental Illness, Netherlands Organization for Scientific Research (NWO) [ERC-230374]
- MagW/ZonMW [Middelgroot-911-09-032]
- Center for Medical Systems Biology (CSMB, NWO Genomics)
- NBIC/BioAssist/RK [2008.024]
- Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL) [184.021.007]
- VU University's Institute for Health and Care Research (EMGO+)
- Neuroscience Campus Amsterdam (NCA)
- Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health
- Rutgers University Cell and DNA Repository [NIMH U24 MH068457-06]
- Avera Institute, Sioux Falls, South Dakota (USA)
- National Institutes of Health [NIH R01 HD042157-01A1, MH081802, 1RC2 MH089951, 1RC2 MH089995]
- Royal Netherlands Academy of Science Professor Award [PAH/6635]
- MRC [MC_UU_12013/6] Funding Source: UKRI
- Medical Research Council [MC_UU_12013/6, MC_PC_15018, G9815508] Funding Source: researchfish
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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.
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