Single Nucleotide Polymorphism Heritability of Behavior Problems in Childhood: Genome-Wide Complex Trait Analysis - 21/08/15
, Dorret I. Boomsma, PhD c, d, eAbstract |
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.
Le texte complet de cet article est disponible en PDF.Key Words : genome-wide complex trait analysis (GCTA), heritability, children, behavior problems
Plan
| This article is discussed in an editorial by Drs. Philip Asherson and Paul F. O'Reilly on page 702. |
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| The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the Erasmus University Rotterdam, School of Law and Faculty of Social Sciences, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam, and the Stichting Trombosedienst en Artsenlaboratorium Rijnmond (STAR), Rotterdam. The authors gratefully acknowledge the contribution of general practitioners, hospitals, midwives, and pharmacies in Rotterdam. The first phase of the Generation R Study is made possible by financial support from: Erasmus Medical Centre, Rotterdam, Erasmus University Rotterdam, and the Netherlands Organization for Health Research and Development (ZonMw). H. Tiemeier, MD, PhD, was supported by NOW-ZonMW VIDI (grant no. 017.106.370). M.H. van IJzendoorn, PhD, and M.J. Bakermans-Kranenburg, PhD, were supported by the Dutch Ministry of Education, Culture, and Science and the Netherlands Organization for Scientific Research (Gravitation program, SPINOZA, VICI). Viara Mileva-Seitz, PhD, was supported by NWO RUBICON prize no. 446-11-023. M.J. Bakermans-Kranenburg, PhD, H. Tiemeier, MD, PhD, F.C. Verhulst, MD, PhD, and M.H. van IJzendoorn, PhD, are also members of the Consortium on Individual Development, which is funded through the Gravitation program of the Dutch Ministry of Education, Culture, and Science and the Netherlands Organization for Scientific Research (NWO grant no. 024.001.003). |
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| Disclosure: Dr. Verhulst has received remuneration as contributing author of the Achenbach System of Empirically Based Assessment (ASEBA). Drs. Pappa, Mileva-Seitz, Hottenga, Bakermans-Kranenburg, Bartels, van Beijsterveldt, Jaddoe, Middeldorp, Rippe, Rivadeneira, Tiemeier, van IJzendoorn, Boomsma, and Ms. Fedko report no biomedical financial interests or potential conflicts of interest. |
Vol 54 - N° 9
P. 737-744 - septembre 2015 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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