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Munafò MR, Matheson IJ, Flint J. Association of the DRD2 gene Taq1A polymorphism and alcoholism: a meta-analysis of case-control studies and evidence of publication bias. Mol Psychiatry 12: 454-461

Department of Experimental Psychology, University of Bristol, Bristol, UK.
Molecular Psychiatry (Impact Factor: 15.15). 05/2007; 12(5):454-61. DOI: 10.1038/sj.mp.4001938
Source: PubMed

ABSTRACT We investigated the association of the dopamine D2 receptor (DRD2) Taq1A polymorphism and alcoholism, using meta-analytic techniques, and specifically undertook an investigation of possible publication bias. Potential publication bias represents a genuine risk to the integrity of published research, but its impact has rarely been documented. We observed a small effect of the DRD2 Taq1A polymorphism on risk of alcoholism, indicating increased alcoholism in individuals possessing the A1 allele of the Taq1A polymorphism (OR=1.21, 95% CI 1.13-1.30, P<0.001). This association remained significant when data from samples of European and East Asian ancestry were analyzed separately. We did not find evidence for association in high-severity alcoholism compared to low-severity alcoholism. Removing the first published study significantly reduced the magnitude of the pooled effect size estimate, although the association remained significant. In addition, we observed evidence for possible publication bias and for the strength of individual study effect size to be inversely related to year of publication. These results support the association of the DRD2 Taq1A polymorphism with alcoholism. This conclusion is qualified by the possibility of publication bias in the literature and the observed between-study heterogeneity, which indicates that the observed association may differ in strength between populations or may not exist at all in some populations.

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    • "genotype (hetero-or homozygous for A1) (Blum et al. 1990). Two meta-analyses of Caucasian alcoholics and controls nonetheless support a link between the A1 allele and alcoholism (Munafo et al. 2007; Smith et al. 2008). Currently, the A1 allele is recognized as a risk factor for alcoholism (Agrawal et al. 2012). "
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    ABSTRACT: The ankyrin repeat and kinase domain containing 1 (ANKK1) TaqIA polymorphism has been extensively studied as a marker of the gene for dopamine receptor D2 (DRD2) in addictions and other dopamine-associated traits. In vitro mRNA and protein studies have shown a potential connection between ANKK1 and the dopaminergic system functioning. Here, we have investigated whether Ankk1 expression in the brain is regulated by treatment with dopaminergic agonists. We used quantitative RT-PCR of total brain and Western blots of specific brain areas to study Ankk1 in murine brain after dopaminergic treatments. We found that Ankk1 mRNA was upregulated after activation of D1R-like dopamine receptors with SKF38393 (2.660 ± 1.035-fold; t: 4.066, df: 11, P = 0.002) and apomorphine (2.043 ± 0.595-fold; t: 3.782, df: 8, P = 0.005). The D2R-like agonist quinelorane has no effect upon Ankk1 mRNA (1.004 ± 0.580-fold; t: 0.015, df: 10, P = 0.9885). In contrast, mice treatment with the D2R-like agonists 7-OH-DPAT and aripiprazole caused a significant Ankk1 mRNA downregulation (0.606 ± 0.057-fold; t: 2.786, df: 10, P = 0.02 and 0.588 ± 0.130-fold; t: 2.394, df: 11, P = 0.036, respectively). With respect the Ankk1 proteins profile, no effects were found after SKF38393 (t: 0.54, df: 2, P = 0.643) and Quinelorane (t: 0.286, df: 8, P = 0.782) treatments. In contrast, the D2R-like agonist 7-OH-DPAT (±) caused a significant increment of Ankk1 in the striatum (t: 2.718, df: 7; P = 0.03) when compared to the prefrontal cortex. The activation of D1R-like and D2-R-like leads to opposite transcriptional regulation of Ankk1 by specific pathways.
    Neurotoxicity Research 07/2015; DOI:10.1007/s12640-015-9545-9 · 3.15 Impact Factor
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    • "Among these, the Taq1A polymorphism (rs1800497) of the DRD2 gene is a substitution located in a noncoding region of the DRD2 locus. The A1 allele (as opposed to the A2 allele) of this polymorphism was shown to be robustly associated with alcohol dependence through a meta-analysis (Munafo et al., 2007). A previous metaanalysis of the association between this DRD2 polymorphism and substance dependence (Munafò et al., 2009). "
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    ABSTRACT: Previous neuroscientific studies have shown that the dopaminergic system plays an important role in creative potential measured by divergent thinking (CPMDT), emotional control, and motivational state. However, although associations between two of these four components have been previously established (e.g., the association between CPMDT and emotional control, the association between CPMDT and motivational state, etc.), the interactions between these four remain unknown. The purpose of this study was to reveal these interactions using path analyses. The Taq1A polymorphism of the dopamine D2 receptor (DRD2) gene was used for this purpose. For measuring emotional intelligence (EI), we used the Japanese version of the Emotional Intelligence Scale. CPMDT was measured using the S-A creativity test. Motivational state was measured using the Vigor subscale of the Japanese version of the Profile of Mood Scale (POMS). Data from 766 healthy, right-handed individuals (426 men and 340 women; 20.7 ± 1.9 years of age) were used in this study. There were significant and robust positive relationships among measures of CPMDT, EI, and motivational state across sex. In addition, the polymorphism of the DRD2 gene was significantly associated with EI, specifically in females. Path analysis in females indicates that the model in which (a) the DRD2 polymorphism primarily facilitates EI, (b) EI in turn facilitates CPMDT and leads to a better motivational state, and (c) a better motivational state also directly facilitates CPMDT explains the data in the most accurate manner. This study suggested a comprehensive picture of the cascade of the associations among dopamine, EI, motivational state, and CPMDT at least in females.
    Frontiers in Psychology 07/2015; 6:912. DOI:10.3389/fpsyg.2015.00912 · 2.80 Impact Factor
    • "MOLECuLAR GENETIC FINDINGS SuPPORTING EvOCATIvE rGE To our knowledge, only two molecular genetic studies have examined the link between children's genotype and the parenting they experience, while also taking into account the parents' genotype in order to rule out passive rGE (Mills-Koonce et al., 2007; Pener- Tessler et al., 2013). Mills-Koonce and colleagues (2007) demonstrated that children who were carriers of A1 allele of the Taq1A polymorphism of the dopamine receptor D2 (DRD2), which has been associated with decreased reward sensitivity and addiction (Munafò, Clark, Johnstone, Murphy, & Walton, 2004; Munafò, Matheson, & Flint, 2007), exhibited greater negative mood during parent– child interactions and had mothers who were less sensitive. Importantly, the authors also demonstrated that the mothers' DRD2 genotype was not associated with maternal sensitivity or with the child's mood, thus ruling out the possibility of passive rGE that is based on mothers and children sharing their DRD2 genotype. "
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    ABSTRACT: The study of socialization substantially contributes to identification of the underpinnings of personality and psychopathology, and to the promotion of children’s healthy development and well-being. However, the lion’s share of psychological research to date has investigated the environment as the force shaping development, and has therefore focused on the “nurture” while neglecting the “nature” part of the equation. Indeed, even though the age-old debate of nature versus nurture has turned into the realization that nature and nurture contribute to development synergistically (Plomin & Asbury, 2005), the integration of knowledge from quantitative genetic and, later, molecular studies into psychological research is only beginning to happen in a new wave of studies. In this chapter we review some of these studies and attempt to provide a glimpse of the intricate web of influences that mold child development. Throughout their development, children are exposed to many socialization agents, including siblings, peers, school, and the media. However, children’s first caregiving figures are usually the parents, who are considered to have long-standing effects on child development (Belsky & de Haan, 2011). Most of psychology’s grand theories allocated an important role to parents in children’s personality and psychopathology development (for historical reviews, see Grusec & Kuczynski, 1997; Maccoby, 1992). Therefore, many researchers have chosen to study the influence of parental behavior on child outcomes. As a consequence, most of the research reviewed in this chapter concerns parents. We start by discussing parenting, and the meaning of parenting effects on children’s development in light of gene–environment correlation (rGE; when the environment to which the individual is exposed is associated with his or her genotype through passive or active processes) and gene–environment interaction (G × E; when an outcome is affected by the nonadditive contributions of the developing person’s genetics and his or her environment). We present research from both quantitative genetic and molecular research designs. Quantitative genetic designs rely on genetic similarities between family members in order to estimate genetic and environmental effects on a variable (e.g., temperament). Molecular genetic designs look for associations between a variable of interest (e.g., parenting) and DNA variation across individuals (work reviewed in this chapter typically deals with genes that relate to the modulation of brain processes that involve the activity of dopamine, serotonin, oxytocin, and vasopressin, which have all been associated with social behavior in different species). We then describe epigenetic and other processes in which environmental effects can leave their mark on the developing person through their effect on biological factors. Finally, we discuss both G × E and rGE with regard to socialization processes outside the home, most notably school and peers. Table 15.1 provides a description of key genetic concepts relevant to socialization.
    Handbook of Socialization: Theory and research, 2 edited by J. E. Grusec & P. D. Hastings, 01/2015; Guilford Press.
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