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



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.



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.



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.
Biological Psychology, VU University, Amsterdam, The Netherlands.
Michel G
MG
Nivard
Department of Psychological Sciences, University of Liverpool, Liverpool, UK.|MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.|UK Centre for Tobacco and Alcohol Studies, School of Experimental Psychology, University of Bristol, Bristol, UK.
Suzanne H
SH
Gage
Biological Psychology, VU University, Amsterdam, The Netherlands.|Amsterdam Public Health, Amsterdam, The Netherlands.
Jouke J
JJ
Hottenga
Biological Psychology, VU University, Amsterdam, The Netherlands.
Catharina E M
CEM
van Beijsterveldt
Biological Psychology, VU University, Amsterdam, The Netherlands.
Abdel
A
Abdellaoui
Biological Psychology, VU University, Amsterdam, The Netherlands.|Amsterdam Public Health, Amsterdam, The Netherlands.
Meike
M
Bartels
Biological Psychology, VU University, Amsterdam, The Netherlands.|Amsterdam Public Health, Amsterdam, The Netherlands.
Bart M L
BML
Baselmans
Biological Psychology, VU University, Amsterdam, The Netherlands.|Amsterdam Public Health, Amsterdam, The Netherlands.
Lannie
L
Ligthart
MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.|Department of Language and Genetics, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands.
Beate St
BS
Pourcain
Biological Psychology, VU University, Amsterdam, The Netherlands.|Amsterdam Public Health, Amsterdam, The Netherlands.|Amsterdam Neuroscience, Amsterdam, The Netherlands.
Dorret I
DI
Boomsma
MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.|UK Centre for Tobacco and Alcohol Studies, School of Experimental Psychology, University of Bristol, Bristol, UK.
Marcus R
MR
Munafò
Biological Psychology, VU University, Amsterdam, The Netherlands.|Amsterdam Neuroscience, Amsterdam, The Netherlands.|Department of Child and Adolescent Psychiatry, GGZ inGeest/ VU University Medical Centre, Amsterdam, The Netherlands.
Christel M
CM
Middeldorp
D000293:Adolescent; D001008:Anxiety Disorders / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D002648:Child; D019955:Conduct Disorder / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D003866:Depressive Disorder / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D020412:Multifactorial Inheritance; D009426:Netherlands; D012042:Registries; D018570:Risk Assessment; D012559:Schizophrenia / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D006113:United Kingdom
developmental psychiatry; genetic epidemiology; schizophrenia prodrome