title: Single Nucleotide Polymorphism Heritability of Behavior Problems in Childhood: Genome-Wide Complex Trait Analysis.
abstract: OBJECTIVE
  Genetic factors contribute to individual differences in behavior problems. In children, genome-wide association studies (GWAS) have yielded the first suggestive results when aiming to identify genetic variants that explain heritability, but the proportion of genetic variance that can be attributed to common single nucleotide polymorphisms (SNPs) remains to be determined, as only a few studies have estimated SNP heritability, with diverging results.
  
  
  METHODS
  Genomic-relationship-matrix restricted maximum likelihood (GREML) as implemented in the software Genome-Wide Complex Trait Analysis (GCTA) was used to estimate SNP heritability (SNP h(2)) for multiple phenotypes within 4 broad domains of children's behavioral problems (attention-deficit/hyperactivity symptoms, internalizing, externalizing, and pervasive developmental problems) and cognitive function. We combined phenotype and genotype data from 2 independent, population-based Dutch cohorts, yielding a total number of 1,495 to 3,175 of 3-, 7-, and 9-year-old children.
  
  
  RESULTS
  Significant SNP heritability estimates were found for attention-deficit/hyperactivity symptoms (SNP h(2) = 0.37-0.71), externalizing problems (SNP h(2) = 0.44), and total problems (SNP h(2) = 0.18), rated by mother or teacher. Sensitivity analyses with exclusion of extreme cases and quantile normalization of the phenotype data decreased SNP h(2) as expected under genetic inheritance, but they remained statistically significant for most phenotypes.
  
  
  CONCLUSIONS
  We provide evidence of the influence of common SNPs on child behavior problems in an ethnically homogenous sample. These results support the continuation of large GWAS collaborative efforts to unravel the genetic basis of complex child behaviors.
authors: School of Pedagogical and Educational Sciences, Erasmus University Rotterdam, Rotterdam, The Netherlands and the Generation R Study Group, Erasmus Medical Center.
authors: Irene
authors: I
authors: Pappa
authors: VU University Amsterdam.
authors: Iryna O
authors: IO
authors: Fedko
authors: Generation R Study Group, Erasmus Medical Center; Centre for Child and Family Studies.
authors: Viara R
authors: VR
authors: Mileva-Seitz
authors: VU University Amsterdam; EMGO(+) Institute for Health and Care Research, VU University Medical Center, Amsterdam.
authors: Jouke-Jan
authors: JJ
authors: Hottenga
authors: Centre for Child and Family Studies.
authors: Marian J
authors: MJ
authors: Bakermans-Kranenburg
authors: VU University Amsterdam; EMGO(+) Institute for Health and Care Research, VU University Medical Center, Amsterdam; Neuroscience Campus Amsterdam.
authors: Meike
authors: M
authors: Bartels
authors: VU University Amsterdam.
authors: Catharina E M
authors: CE
authors: van Beijsterveldt
authors: Generation R Study Group, Erasmus Medical Center; Erasmus Medical Center.
authors: Vincent W V
authors: VW
authors: Jaddoe
authors: VU University Amsterdam; Neuroscience Campus Amsterdam.
authors: Christel M
authors: CM
authors: Middeldorp
authors: Centre for Child and Family Studies.
authors: Ralph C A
authors: RC
authors: Rippe
authors: Erasmus Medical Center.
authors: Fernando
authors: F
authors: Rivadeneira
authors: Generation R Study Group, Erasmus Medical Center; Erasmus Medical Center; Erasmus Medical Center-Sophia Children's Hospital, Rotterdam.
authors: Henning
authors: H
authors: Tiemeier
authors: Generation R Study Group, Erasmus Medical Center; Erasmus Medical Center-Sophia Children's Hospital, Rotterdam.
authors: Frank C
authors: FC
authors: Verhulst
authors: School of Pedagogical and Educational Sciences, Erasmus University Rotterdam, Rotterdam, The Netherlands and the Generation R Study Group, Erasmus Medical Center; Centre for Child and Family Studies, Leiden University, Leiden, The Netherlands. Electronic address: vanijzen@fsw.leidenuniv.nl.
authors: Marinus H
authors: MH
authors: van IJzendoorn
authors: VU University Amsterdam; EMGO(+) Institute for Health and Care Research, VU University Medical Center, Amsterdam; Neuroscience Campus Amsterdam.
authors: Dorret I
authors: DI
authors: Boomsma
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000523:psychology*; D000067290:Behavior Rating Scale; D002648:Child; D002675:Child, Preschool; D003071:Cognition; D015331:Cohort Studies; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide; D000066553:Problem Behavior / Q000523:psychology*; D011569:Psychiatric Status Rating Scales; D019655:Quantitative Trait, Heritable; D012984:Software
keywords: behavior problems; children; genome-wide complex trait analysis (GCTA); heritability