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DAT1 and DRD4 genes involved in key dimensions of adult ADHD

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Abstract

Attention-deficit hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder often persisting in adulthood. Genetic studies of ADHD mainly focused on the Dopamine Transporter (DAT1) and the Dopamine Receptor 4 (DRD4) genes. Nevertheless, polymorphisms of these genes explain only a small fraction of the assigned risk, suggesting that intermediate dimensions and environmental factors should also be considered. We investigated in 77 adult ADHD subjects compared to 474 controls, how polymorphisms within the genes coding for DAT1 (40-bp VNTR in 3′UTR), the Dopamine Receptor 2 (DRD2) (rs1799732) and DRD4 (48-bp VNTR in exon 3), may modulate the expression of the disorder. By genotyping DAT1, we detected a new 9.5R allele showing a deletion of 40 bp and also an insertion of 19 bp compared to the 10R allele. This novel allele was found to be significantly protective for ADHD (p < 0.0001). Another significant difference was found in the distribution of DRD4 48-bp VNTR 6R allele when comparing patients and controls (p = 0.0007). In addition significant results were also found for DAT1 9.5R allele, which was associated with impulsiveness (p = 1.98 × 10−4) and trait anger scores (p = 7.66 × 10−4). Moreover, impulsiveness scores were partly modulated by an interaction between the DRD4 48-bp VNTR 6R allele and childhood maltreatment (p = 0.01), however, this result did not resist correction for multiple comparisons. Altogether, our results show the putative involvement of DAT1 and DRD4 genes in the aetiology of ADHD with a main role in modulation of key dimensions of the disorder.

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Authors and Affiliations

  1. Department of Psychiatry, University of Geneva, Geneva, Switzerland

    R. Hasler, A. Salzmann, T. Bolzan, P. Giannakopoulos & N. Perroud

  2. Neurocenter, Geneva, Switzerland

    R. Hasler & T. Bolzan

  3. Department of Mental Health and Psychiatry, University Hospitals of Geneva, Geneva, Switzerland

    J. Zimmermann, P. Baud, P. Giannakopoulos & N. Perroud

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  1. R. Hasler
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Correspondence to R. Hasler.

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10072_2014_2051_MOESM1_ESM.docx

Supplementary Figure S1 Visualisation of new repeat allele 9.5R (454 bp) together with allele 9R (435 bp) and allele 10R (475 bp) on a 1.5 % agarose gel with a 50-bp DNA ladder on the left and a 100-bp DNA ladder on the right. (PPTX 45 kb)

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Hasler, R., Salzmann, A., Bolzan, T. et al. DAT1 and DRD4 genes involved in key dimensions of adult ADHD. Neurol Sci 36, 861–869 (2015). https://doi.org/10.1007/s10072-014-2051-7

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  • DOI: https://doi.org/10.1007/s10072-014-2051-7

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