No association of the −521 C/T polymorphism in the promoter of DRD4 with novelty seeking

Ekelund, Jesper; Suhonen, Jaana; Järvelin, Marjo‐Riitta; Peltonen, Leena; Lichtermann, Dirk

doi:10.1038/sj.mp.4000943

Cited by 30 publications

(25 citation statements)

References 18 publications

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“…The lack of LD between the −521 and −616 SNPs in African Americans is in contrast to the strong LD recently observed between the −521 SNP and the exon III 48-bp repeat in the Finnish population. 21 We found no significant differences between the CG and GG genotypes for the C −616G polymorphism and between the CT and TT genotypes for the C −521T polymorphism among any of the personality dimensions. Similar to previous studies we assumed a dominant model and combined the genotype categories for the analyses.…”

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confidence: 63%

“…13,14,21 We note that allele frequency differences between ethnic populations can be a confounder in association studies if not controlled for, 28,29 especially genetic association studies on the African American population, which is highly heterogeneous due to its African ancestry and recent admixture with European Americans. However the likelihood that our finding is spurious due to population stratification is very low because the allele frequencies for the two SNPs were consistent with frequencies previously described in two other ethnic groups.…”

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confidence: 99%

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DRD4 promoter SNPs and gender effects on Extraversion in African Americans

et al. 2002

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There is strong evidence for genetic influences on personality traits. Interest in one such gene, the dopamine D4 receptor (DRD4) grew after an exon III polymorphism was associated with Novelty Seeking and related measures of Extraversion. However, the findings were not confirmed in later studies. Recently, a −521C/T single nucleotide polymorphism (SNP) within the promoter region of the DRD4 gene was found to be related to Novelty Seeking scores in populations from Japan and Hungary. Since little is known about the role DRD4 plays in personality in other populations we evaluated if two DRD4 promoter SNPs, −521C/T and −616C/G, were related to personality traits in African Americans. Personality traits were measured by the NEO-FFI in 71 unrelated African Americans. Genotyping was performed using PCR-RFLP. Multivariate analyses of variance (MANOVA) were performed to evaluate the effects of gender and −616 and −521 genotypes on personality traits. A significant three-way interaction effect from gender, −616 genotype, and −521 genotype was observed for Extraversion scores (F(1,54) 5.86, P Ͻ 0.02). Subsequent analyses revealed that the association was mainly due to −521C/T genotype among females (P = 0.01). This study provides further evidence that genetic variation within the DRD4 promoter and gender differences contribute to variation in Novelty Seeking behaviors such as Extraversion.

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confidence: 63%

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DRD4 promoter SNPs and gender effects on Extraversion in African Americans

et al. 2002

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“…Again, some observed an association, 57,58 while others did not. 40,42,43,59 A meta-analysis supported the association between NS and the -521 C/T polymorphism. 56 The DRD4 polymorphisms were also studied in relation to the trait of extraversion.…”

Section: Dopaminementioning

confidence: 89%

Genetics of personality: are we making progress?

2003

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For centuries, scientists are intrigued by the differences in personality between individuals. As early as in the ancient Greek civilization, people tried to formulate theories to systematize this diversity. With the increased interest in behavior genetics, personality was also considered a challenging phenotype. From the early start, studies suggested a heritable component in personality. After the successes of molecular genetic studies in unraveling the genetic basis of (mostly) monogenic diseases, the focus shifted towards complex traits, including psychiatric disorders. It was observed in several studies that personality measures differed between patients with psychiatric disorders and healthy controls. Therefore, normal personality was considered a viable endophenotype in the search for genes involved in psychiatric disorders such as affective disorders, ADHD and substance dependence. Genes that were to be found in studies on personality could be candidate genes for particular psychiatric disorders. In the course of time, however the study of genes for personality turned out to be at least as hard as the search for genes involved in other complex disorders. In this review, past studies, present problems and future directions concerning the study of personality genetics are discussed.

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“…Although initial evidence suggested an association between NS and a variable number tandem repeat (VNTR) polymorphism in exon 111 of DRD4 (Benjamin et al, 1996;Ebstein et al, 1996), a recent meta-analysis (Munafo et al, 2008b) refutes this, but demonstrates strong evidence for an association between NS and a cytosine to thymine polymorphism in the DRD4 promoter region (-521OT single nucleotide polymorphism, SNP). For this promoter polymorphism, which is in linkage disequilibrium with the exon III VNTR (Ekelund et al, 2001;Strobel et al, 2002), the C allele is associated with increased transcription levels of up to 40% compared with the T allele in vitro (Okuyama et al, 1999). However, in human post-mortem brain the -5210T SNP was not found to significantly affect DRD4 mRNA expression levels (Simpson et al, 2010), thus whether this SNP is functional is currently not clear.…”

Section: Introductionmentioning

confidence: 99%

Dopamine receptor 4 promoter polymorphism modulates memory and neuronal responses to salience

et al. 2014

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Animal models and human functional imaging data implicate the dopamine system in mediating enhanced encoding of novel stimuli into human memory. A separate line of investigation suggests an association between a functional polymorphism in the promoter region for the human dopamine 4 receptor gene (DRD4) and sensitivity to novelty. We demonstrate, in two independent samples, that the -5210T DRD4 promoter polymorphism determines the magnitude of human memory enhancement for contextually novel, perceptual oddball stimuli in an allele dose-dependent manner. The genotype-dependent memory enhancement conferred by the C allele is associated with increased neuronal responses during successful encoding of perceptual oddballs in the ventral striatum, an effect which is again allele dose-dependent. Furthermore, with repeated presentations of oddball stimuli, this memory advantage decreases, an effect mirrored by adaptation of activation in the hippocampus and substantia nigra/ventral tegmental area in C carriers only. Thus, a dynamic modulation of human memory enhancement for perceptually salient stimuli is associated with activation of a dopaminergic-hippocampal system, which is critically dependent on a functional polymorphism in the DRD4 promoter region.

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No association of the −521 C/T polymorphism in the promoter of DRD4 with novelty seeking

Cited by 30 publications

References 18 publications

DRD4 promoter SNPs and gender effects on Extraversion in African Americans

DRD4 promoter SNPs and gender effects on Extraversion in African Americans

Genetics of personality: are we making progress?

Dopamine receptor 4 promoter polymorphism modulates memory and neuronal responses to salience

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