title: Single Nucleotide Polymorphism Heritability of a General Psychopathology Factor in Children.
abstract: Co-occurrence of mental disorders is commonly observed, but the etiology underlying this observation is poorly understood. Studies in adolescents and adults have identified a general psychopathology factor associated with a high risk for different psychiatric disorders. We defined a multi-informant general psychopathology factor in school-aged children and estimated its single nucleotide polymorphism (SNP) heritability. The goal was to test the hypothesis that child behavioral and emotional problems are under the influence of highly pleiotropic common autosomal genetic variants that nonspecifically increase the risk for different dimensions of psychopathology.
  
  
  
  Children from the Generation R cohort were repeatedly assessed between ages 6 to 8 years. Child behavior problems were reported by parents, teachers, and children. Confirmatory factor analysis estimated a general psychopathology factor across informants using various psychiatric problem scales. Validation of the general psychopathology factor was based on IQ and temperamental measures. Genome-wide complex trait analysis (GCTA) was used to estimate the SNP heritability (N = 2,115).
  
  
  
  The general psychopathology factor was associated with lower IQ, higher negative affectivity, and lower effortful control, but not with surgency. Importantly, the general psychopathology factor showed a significant SNP heritability of 38% (SE = 0.16, p = .008).
  
  
  
  Common autosomal SNPs are pleiotropically associated with internalizing, externalizing, and other child behavior problems, and underlie a general psychopathology factor in childhood.
authors.affiliation: Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Alexander
authors.initials: A
authors.lastname: Neumann
authors.affiliation: School of Pedagogical and Educational Sciences, Erasmus University Rotterdam.
authors.forename: Irene
authors.initials: I
authors.lastname: Pappa
authors.affiliation: University of Chicago, Chicago, IL.
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Lahey
authors.affiliation: Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Frank C
authors.initials: FC
authors.lastname: Verhulst
authors.affiliation: Erasmus Medical Center, Rotterdam.
authors.forename: Carolina
authors.initials: C
authors.lastname: Medina-Gomez
authors.affiliation: Erasmus Medical Center, Rotterdam.
authors.forename: Vincent W
authors.initials: VW
authors.lastname: Jaddoe
authors.affiliation: Center for Child and Family Studies, Leiden University, Leiden, the Netherlands.
authors.forename: Marian J
authors.initials: MJ
authors.lastname: Bakermans-Kranenburg
authors.affiliation: Duke University, Durham, NC.
authors.forename: Terrie E
authors.initials: TE
authors.lastname: Moffitt
authors.affiliation: Center for Child and Family Studies, Leiden University, Leiden, the Netherlands.
authors.forename: Marinus H
authors.initials: MH
authors.lastname: van IJzendoorn
authors.affiliation: Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands. Electronic address: h.tiemeier@erasmusmc.nl.
authors.forename: Henning
authors.initials: H
authors.lastname: Tiemeier
mesh_terms: D002648:Child; D002652:Child Behavior; D005260:Female; D058685:Genetic Pleiotropy; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000235:genetics* / Q000503:physiopathology*; D020641:Polymorphism, Single Nucleotide; D000066553:Problem Behavior; D019655:Quantitative Trait, Heritable
keywords: SNP heritability; child behavior; comorbidity; genetic pleiotropy; psychopathology