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

Abstract

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..