title: NCAM1-TTC12-ANKK1-DRD2 gene cluster and the clinical and genetic heterogeneity of adults with ADHD.
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.
authors.affiliation: Department of Genetics, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.|ADHD Outpatient Program-Adult Division, Hospital de Clínicas, de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Nina R
authors.initials: NR
authors.lastname: Mota
authors.affiliation: Department of Genetics, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.|ADHD Outpatient Program-Adult Division, Hospital de Clínicas, de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Diego L
authors.initials: DL
authors.lastname: Rovaris
authors.affiliation: Department of Genetics, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.|ADHD Outpatient Program-Adult Division, Hospital de Clínicas, de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Djenifer B
authors.initials: DB
authors.lastname: Kappel
authors.affiliation: ADHD Outpatient Program-Adult Division, Hospital de Clínicas, de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Felipe A
authors.initials: FA
authors.lastname: Picon
authors.affiliation: ADHD Outpatient Program-Adult Division, Hospital de Clínicas, de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Eduardo S
authors.initials: ES
authors.lastname: Vitola
authors.affiliation: ADHD Outpatient Program-Adult Division, Hospital de Clínicas, de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Carlos A I
authors.initials: CA
authors.lastname: Salgado
authors.affiliation: ADHD Outpatient Program-Adult Division, Hospital de Clínicas, de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Rafael G
authors.initials: RG
authors.lastname: Karam
authors.affiliation: ADHD Outpatient Program-Adult Division, Hospital de Clínicas, de Porto Alegre, Porto Alegre, Brazil.|Department of Psychiatry, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Rohde
authors.affiliation: ADHD Outpatient Program-Adult Division, Hospital de Clínicas, de Porto Alegre, Porto Alegre, Brazil.|Department of Psychiatry, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Eugenio H
authors.initials: EH
authors.lastname: Grevet
authors.affiliation: Department of Genetics, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.|ADHD Outpatient Program-Adult Division, Hospital de Clínicas, de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Claiton H D
authors.initials: CH
authors.lastname: Bau
keywords: attention deficit/hyperactivity disorder; comorbidity; dopamine receptor; personality