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Evidence for a gene–gene interaction in predicting children's behavior problems: Association of serotonin transporter short and dopamine receptor D4 long genotypes with internalizing and externalizing behaviors in typically developing 7-year-olds

Published online by Cambridge University Press:  11 October 2007

Louis A. Schmidt ,
Nathan A. Fox  and
Dean H. Hamer
Louis A. Schmidt*
Affiliation:
McMaster University
Nathan A. Fox
Affiliation:
University of Maryland
Dean H. Hamer
Affiliation:
National Institutes of Health
*
Address correspondence and reprint requests to: Louis A. Schmidt, Department of Psychology, Neuroscience and Behaviour, 1280 Main Street West, McMaster University, Hamilton, Ontario L8S 4K1, Canada; E-mail: schmidtl@mcmaster.ca.
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Abstract

Recent work on the molecular genetics of complex traits in typical and atypical human development has focused primarilyon associations of single genes with behavior. Disparate literature suggests that the presence of one or two copies of the short allele of the serotonin transporter (5-HTT) gene and the long allele (7-repeat allele) version of the dopamine receptor D4 (DRD4) gene predicts internalizing- and externalizing-related behaviors, respectively. Apparently for the first time in the extant literature, we report a gene–gene statistical interaction on behavior problems in a group of typically developing children at age 7. DNA was extracted from buccal cells collected from 108 children and genotyped for short and long alleles of the 5-HTT gene and the short (2–5 repeats) versus long (6–8 repeats) allele of the DRD4 gene. Mothers completed the Child Behavior Checklist. As predicted, children with one or two copies of the short allele of the 5-HTT gene and the long allele version of the DRD4 gene exhibited significantly more internalizing and externalizing behaviors at age 7 than children with other combinations of the 5-HTT and DRD4 short and long genotypes. As well, children with the 5-HTT long and DRD4 long genotypes had the lowest reported scores on internalizing and externalizing behaviors at age 7, suggesting that the presence of the 5-HTT long genotype may serve as a protective factor against these behaviors in children with the long DRD4 genotype. Implications of these findings for understanding cumulative biological risk and protective factors in childhood behavior problems and psychopathology are discussed.

Type
Research Article
Information
Development and Psychopathology , Volume 19 , Issue 4 , Fall 2007 , pp. 1105 - 1116
Copyright
Copyright © Cambridge University Press 2007

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