Single Nucleotide Polymorphism Heritability of Behavior Problems in Childhood: Genome-Wide Complex Trait Analysis

I. Pappa, I.O. Fedko, V.R. Mileva-Seitz, J.J. Hottenga, M.J. Bakermans-Kranenburg, M. Bartels, C.E.M. van Beijsterveldt, V.W.V. Jaddoe, C.M. Middeldorp, R.C.A. Rippe, F. Rivadeneira, H. Tiemeier, F.C. Verhulst, M.H. van IJzendoorn, D.I. Boomsma

Research output: Contribution to JournalArticleAcademicpeer-review


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. Method: 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 h2) 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 h2 = 0.37-0.71), externalizing problems (SNP h2 = 0.44), and total problems (SNP h2 = 0.18), rated by mother or teacher. Sensitivity analyses with exclusion of extreme cases and quantile normalization of the phenotype data decreased SNP h2 as expected under genetic inheritance, but they remained statistically significant for most phenotypes. Conclusion: 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.
Original languageEnglish
Pages (from-to)737-744
Number of pages8
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Issue number9
Publication statusPublished - 2015

Cohort Studies

  • Netherlands Twin Register (NTR)


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