Cited by 25Attention Deficit Hyperactivity DisorderNeurotransmitter Receptor Influence on BehaviorGenetic Associations and Epidemiology

NCAM1‐TTC12‐ANKK1‐DRD2 gene cluster and the clinical and genetic heterogeneity of adults with ADHD

Mota, Nina R., Rovaris, Diego L., Kappel, Djenifer B., Picon, Felipe A., Vitola, Eduardo S., Salgado, Carlos A. I., Karam, Rafael G., Rohde, Luis A. +2 more·2015·American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

Abstract

Dysfunctions of the dopaminergic system have been implicated on the etiology of Attention Deficit/Hyperactivity Disorder (ADHD). Meta‐analyses addressing the association of the dopamine receptor D2 (DRD2) gene and ADHD were inconclusive due to excessive heterogeneity across studies. Both the great phenotypic heterogeneity of ADHD and the complexity of the genomic region where DRD2 is located could contribute to the inconsistent findings. Most previous DRD2 studies focused on the well‐known Taq1A (rs1800497) SNP, which is actually placed in a neighbor gene (ANKK1). These two genes, together with NCAM1 and TTC12, form the NTAD gene cluster on Chr11q22–23. In order to address the reasons for the high heterogeneity previously reported on DRD2 effects on ADHD, this study investigates the role of NTAD variants on ADHD susceptibility in adults and on the modulation of comorbidity and personality profiles in these patients. Functional polymorphisms from NTAD were analyzed, both individually and in haplotypes, on a sample of 520 adults with ADHD and 630 non‐ADHD controls. No direct association of NTAD variants with ADHD susceptibility itself was observed. However, different NTAD polymorphisms and haplotypes were associated to various phenotypes relevant to the clinical heterogeneity of ADHD, including Major Depressive Disorder, Generalized Anxiety Disorder, and Harm Avoidance and Persistence temperament scores. Therefore, these findings represent a possible explanation for the multiple conflicting findings regarding polymorphisms in this genomic region in psychiatry. The NTAD cluster may comprise a variety of independent molecular influences on various brain and behavior characteristics eventually associated with ADHD comorbidities and personality traits. © 2015 Wiley Periodicals, Inc.

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Crossref · 10.1002/ajmg.b.32317

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Authors
Mota, N. R., Rovaris, D. L., Kappel, D. B., Picon, F. A., Vitola, E. S., Salgado, C. A. I., Karam, R. G., Rohde, L. A., Grevet, E. H., & Bau, C. H. D.
Affiliations
  • Universidade Federal do Rio Grande do Sul (BR)
  • Hospital de Clínicas de Porto Alegre (BR)
  • ADHD Outpatient Program—Adult Division Hospital de Clínicas de Porto Alegre Porto Alegre Brazil
Corresponding author
Bau, Claiton H. D.
Venue
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Publisher
Wiley
Published
2015-05-18
Volume
168
Issue
6
Pages
433-444
ISSN
  • 1552-4841 (ISSN-L)
  • 1552-485X
OpenAlex
W1500570688
Cited by
25
References
93
Citations by year
2026: 3 · 2025: 7 · 2024: 1 · 2022: 3 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 1
FWCI
1.09
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico
  • Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
attention deficit hyperactivity disorder, adult ADHD, CD56, ANKK1, DRD2, dopamine D2 receptor, genetic heterogeneity, haplotypes, functional polymorphisms, major depressive disorder, generalized anxiety disorder, harm avoidance, persistence, personality traits, ADHD comorbidity, dopaminergic system

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