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

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. 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.
LanguageEnglish
Pages737-744
Number of pages8
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Volume54
Issue number9
DOIs
Publication statusPublished - 2015

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Single Nucleotide Polymorphism
Genome
Phenotype
Genome-Wide Association Study
Child Behavior
Problem Behavior
Individuality
Cognition
Software
Genotype
Mothers
Population

Cite this

@article{a775f048186b416eb0d358d22ed250bc,
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. 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.",
author = "I. Pappa and I.O. Fedko and V.R. Mileva-Seitz and J.J. Hottenga and M.J. Bakermans-Kranenburg and M. Bartels and {van Beijsterveldt}, C.E.M. and V.W.V. Jaddoe and C.M. Middeldorp and R.C.A. Rippe and F. Rivadeneira and H. Tiemeier and F.C. Verhulst and {van IJzendoorn}, M.H. and D.I. Boomsma",
year = "2015",
doi = "10.1016/j.jaac.2015.06.004",
language = "English",
volume = "54",
pages = "737--744",
journal = "Journal of the American Academy of Child and Adolescent Psychiatry",
issn = "0890-8567",
publisher = "Elsevier Limited",
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}

Single Nucleotide Polymorphism Heritability of Behavior Problems in Childhood: Genome-Wide Complex Trait Analysis. / Pappa, I.; Fedko, I.O.; Mileva-Seitz, V.R.; Hottenga, J.J.; Bakermans-Kranenburg, M.J.; Bartels, M.; van Beijsterveldt, C.E.M.; Jaddoe, V.W.V.; Middeldorp, C.M.; Rippe, R.C.A.; Rivadeneira, F.; Tiemeier, H.; Verhulst, F.C.; van IJzendoorn, M.H.; Boomsma, D.I.

In: Journal of the American Academy of Child and Adolescent Psychiatry, Vol. 54, No. 9, 2015, p. 737-744.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - Single Nucleotide Polymorphism Heritability of Behavior Problems in Childhood: Genome-Wide Complex Trait Analysis

AU - Pappa, I.

AU - Fedko, I.O.

AU - Mileva-Seitz, V.R.

AU - Hottenga, J.J.

AU - Bakermans-Kranenburg, M.J.

AU - Bartels, M.

AU - van Beijsterveldt, C.E.M.

AU - Jaddoe, V.W.V.

AU - Middeldorp, C.M.

AU - Rippe, R.C.A.

AU - Rivadeneira, F.

AU - Tiemeier, H.

AU - Verhulst, F.C.

AU - van IJzendoorn, M.H.

AU - Boomsma, D.I.

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

U2 - 10.1016/j.jaac.2015.06.004

DO - 10.1016/j.jaac.2015.06.004

M3 - Article

VL - 54

SP - 737

EP - 744

JO - Journal of the American Academy of Child and Adolescent Psychiatry

T2 - Journal of the American Academy of Child and Adolescent Psychiatry

JF - Journal of the American Academy of Child and Adolescent Psychiatry

SN - 0890-8567

IS - 9

ER -