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 (GABA_BR1), has recently been cloned and localized to the region of 6p with the strongest support for linkage to RD. GABA_BR1 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 GABA_BR1 receptor gene as a candidate for ADHD as well. In addition, the role of the GABA_B 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..