Attention Deficit Hyperactivity Disorder Candidate Research Articles

Identification of polymorphisms in the GABAB receptor gene and linkage study of attention-deficit hyperactivity disorder

Individuals with attention-deficit hyperactivity disorder (ADHD) are often diagnosed with comorbid reading disabilities (RD) and twin studies have suggested a genetic relationship. Genetic linkage to several chromosome locations has been reported for RD, including a region located on chromosome 6p, near the human leukocyte antigen (HLA) region. The gene for the gamma-aminobutyric acid (GABA) beta receptor 1 gene (GABABR1), has recently been cloned and localized to the region of 6p with the strongest support for linkage to RD. GABABR1 is an interesting candidate gene for RD based on its location and its proposed role in cognition. The genetic link between RD and ADHD supports the GABABR1 receptor gene as a candidate for ADHD as well. In addition, the role of the GABAB receptor in modulating the release of a number of neurotransmitters, including dopamine and norepinephrine, both postulated to be involved in ADHD, suggests that this receptor may play a role in the ADHD phenotype. Based on this hypothesis, we screened this gene for DNA sequence variants. We identified nine DNA sequence variants in a sample of ADHD probands with and without comorbid RD. Three of the common variants were used for linkage analysis to the ADHD phenotype in a sample of 98 families identified through an ADHD proband. We did not observe significant evidence for linkage in our sample. Our findings do not support a role of this gene in ADHD..

Linkage study of two polymorphisms at the dopamine D3 receptor gene and attention-deficit hyperactivity disorder

Data from animal studies suggest that the dopamine D3 receptor gene may have a role in locomotion and behavioral regulation. Therefore, this gene has been suggested as a candidate for attention-deficit hyperactivity disorder (ADHD). The dopamine D3 receptor gene (DRD3) has two common polymorphisms, one in exon I that changes a Serine to Glycine (Ser9Gly) and alters the recognition site for the restriction enzyme MscI [Lannfelt et al., 1992]. The other common polymorphism is located in intron 5 and results in the change of a restriction site for MspI [Griffon et al., 1996]. We investigated the possibility of linkage of the dopamine D3 receptor gene in 100 small, nuclear families consisting of a proband with ADHD, their parents, and affected siblings. We examined the transmission of the alleles of each of these polymorphisms and the haplotypes of both polymorphisms using the transmission disequilibrium test [Spielman et al., 1993]. We did not observe biased transmission of the alleles at either polymorphism or any haplotype. Our findings using this particular sample do not support the role of the dopamine D3 gene in ADHD. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:114–117, 2000. © 2000 Wiley-Liss, Inc.

Linkage study of two polymorphisms at the dopamine D3 receptor gene and attention-deficit hyperactivity disorder

Data from animal studies suggest that the dopamine D3 receptor gene may have a role in locomotion and behavioral regulation. Therefore, this gene has been suggested as a candidate for attention-deficit hyperactivity disorder (ADHD). The dopamine D3 receptor gene (DRD3) has two common polymorphisms, one in exon I that changes a Serine to Glycine (Ser9Gly) and alters the recognition site for the restriction enzyme MscI [Lannfelt et al., 1992]. The other common polymorphism is located in intron 5 and results in the change of a restriction site for MspI [Griffon et al., 1996]. We investigated the possibility of linkage of the dopamine D3 receptor gene in 100 small, nuclear families consisting of a proband with ADHD, their parents, and affected siblings. We examined the transmission of the alleles of each of these polymorphisms and the haplotypes of both polymorphisms using the transmission disequilibrium test [Spielman et al., 1993]. We did not observe biased transmission of the alleles at either polymorphism or any haplotype. Our findings using this particular sample do not support the role of the dopamine D3 gene in ADHD. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:114-117, 2000.