Interactions between the COMT Val108/158Met polymorphism and maternal prenatal smoking predict aggressive behavior outcomes

Department of Psychology, 36 Eagle Row, Emory University, Atlanta, GA 30322, USA.
Biological psychology (Impact Factor: 3.4). 02/2011; 87(1):99-105. DOI: 10.1016/j.biopsycho.2011.02.013
Source: PubMed


The purpose of the current study is to examine the moderating influence of the catechol O methyltransferase gene (COMT) on the maternal prenatal smoking/offspring externalizing disorder relationship. The sample consisted of 430 young adults born between 1981 and 1984 at the Mater Misericordiae Mother's Hospital in Brisbane, Australia, as well as their mothers and peers. Mothers reported their prenatal smoking status during pregnancy, and genetic data was obtained from the youth at a later follow-up in adulthood. The outcome measures in this study were mother and teacher reports of youth attention problems and aggression at age 15, and youth, mother and peer reports of youth attention problems and aggression at age 20 (combined to create latent factors of attention problems and aggression at each age). The COMT Val108/158Met polymorphism (rs4680) significantly interacted with maternal cigarette smoking during pregnancy to predict youth aggressive behavior at ages 15 and 20. This gene-environment interaction was not significant for youth attention problems.

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    • "genes and prenatal tobacco exposure. Prenatal tobacco exposure interacts with fetal MAOA genotype and with several dopaminergic genes, leading to increased offspring externalizing problems in children who were already genetically susceptible (Brennan et al. 2011; Kahn et al. 2003; Langley et al. 2008; Neuman et al. 2007; Wakschlag et al. 2009). There is less evidence for such genotype 9 prenatal tobacco exposure effects for internalizing, although Hsieh et al. (2010) observed an interaction between maternal prenatal passive smoking and a fetal metabolic gene (CYP1A1), which resulted in more offspring internalizing at age two. "
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    ABSTRACT: Maternal smoking during pregnancy (SDP) is associated with increased risk of externalizing and internalizing behaviors in offspring. Two explanations (not mutually exclusive) for this association are direct causal effects of maternal SDP and the effects of genetic and environmental factors common to parents and offspring which increase smoking as well as problem behaviors. Here, we examined the associations between parental SDP and mother rated offspring externalizing and internalizing behaviors (rated by the Child Behavior Checklist/2-3) at age three in a population-based sample of Dutch twins (N = 15,228 pairs). First, as a greater effect of maternal than of paternal SDP is consistent with a causal effect of maternal SDP, we compared the effects of maternal and paternal SDP. Second, as a beneficial effect of quitting smoking before pregnancy is consistent with the causal effect, we compared the effects of SDP in mothers who quit smoking before pregnancy, and mothers who continued to smoke during pregnancy. All mothers were established smokers before their pregnancy. The results indicated a greater effect of maternal SDP, compared to paternal SDP, for externalizing, aggression, overactive and withdrawn behavior. Quitting smoking was associated with less externalizing, overactive behavior, aggression, and oppositional behavior, but had no effect on internalizing, anxious depression, or withdrawn behavior. We conclude that these results are consistent with a causal, but small, effect of smoking on externalizing problems at age 3. The results do not support a causal effect of maternal SDP on internalizing behaviors.
    Full-text · Article · Sep 2015 · Behavior Genetics
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    • "There are no data on asthma. Recently, an interaction between maternal smoking and aggressive behaviour of children at the age of 15 to 20 years was predicted for rs4680 genotype [29]. This underlines the interfering role of the maternal smoking behaviour for the life quality of the child. "
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    ABSTRACT: Objective: Obstructive respiratory diseases, mainly the chronic obstructive pulmonary disease (COPD) and asthma, are associated with functional polymorphisms of xenobiotic-metabolizing enzymes (XMEs). To date, association for obstructive bronchitis has not been described. Material/methods: In this study, we investigated the genotypes from 26 functional polymorphisms of 20 XMEs in children (n, 1028) at the age of 6 years from the German prospective birth cohort study (LISAplus) and analyzed the associations between genotypes and obstructive bronchitis. Results: For the first time, we found noteworthy gene-disease associations for the functional PON1 M55L and EPHX1 H139R polymorphisms and gene-environment associations for the functional COMT V158M and NQO1 P187S polymorphisms after stratification for maternal active smoking behaviour during pregnancy. The noteworthy associations were substantiated by the biological findings that all the risk genotypes belong to genes involved in oxidative stress and code for proteins with a fast enzymatic activity or concomitantly appear in common estrogene-metabolizing pathway (COMT, NQO1). Conclusion: The oxidative stress has to be taken into account in mechanism of the obstructive bronchitis in early childhood. The risk genotypes may serve as risk factors for respiratory obstruction rather than for signs of COPD or asthma.
    Full-text · Article · Jun 2012 · Metabolism: clinical and experimental
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    • "While another study [Neuman et al., 2007] also reported a significant association between the child's DAT1 genotype and ADHD, they observed the findings for the other DAT1 allele (i.e., the 440 allele). Also, the COMT genotype was found to interact with maternal smoking to predict youth aggressive behavior [Brennan et al., 2011]. Here, we report on our examination of the moderating effect of maternal smoking during pregnancy on the association between 5-HTTLPR and emotional problems in a large population-based cohort of European descent, the Generation R Study. "
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    ABSTRACT: Serotonin is involved in the development of neural circuits modulating emotional behavior. The short allele (s) of a polymorphism (5-HTTLPR) of the serotonin transporter gene is a risk factor for psychopathology in the presence of environmental stressors. Maternal smoking is associated with growth restriction of the human fetal brain and adverse effects of nicotine on the developing serotonin system have been documented. We hypothesized that maternal smoking interacts with both child and mother 5-HTTLPR genotype as a risk factor for later child emotional problems. In a sample of n = 1,529 mother-child dyads, smoking habits were assessed by questionnaires during pregnancy. Child emotional problems were measured by the Child Behavior Checklist at the child's age of 3 years. Maternal smoking during pregnancy significantly increased the risk for emotional problems in children carrying the s-allele; β = 0.24, P = 0.03 (mother-report), and β = 0.46, P = 0.001 (father-report). In children heterozygous at 5-HTTLPR and exposed to maternal prenatal smoking (n = 79) risk of emotional problems increased with each additional s-allele the mother carried. The associations between 5-HTTLPR and child emotional problems were not moderated by paternal prenatal smoking. These findings imply that the vulnerability for emotional problems in s-allele carriers may already originate in fetal life.
    Full-text · Article · Apr 2012 · American Journal of Medical Genetics Part B Neuropsychiatric Genetics
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