Excluding linkage between panic disorder and the gamma-aminobutyric acid beta 1 receptor locus in five Icelandic pedigrees.

Abstract

The GABAA receptor subunits are candidate genes for panic disorder because the receptor is the site of action for the anxiolytic effects of the benzodiazepines. We tested for linkage between a tetranucleotide repeat polymorphism at the GABAA beta 1 locus, located on chromosome 4p13-p12, and panic disorder defined by DSM-III-R criteria in 5 Icelandic pedigrees. Both a narrow affection status (definite panic disorder and agoraphobia) and a broad one (including probable cases of these disorders) were tested. With the narrow definition, at a recombination fraction of 0.00, the lod scores in the 5 pedigrees ranged from -3.240 to +0.063, the total score across all 5 pedigrees being -8.299. With the broad definition at the same recombination fraction, the individual lod scores ranged from -2.614 to -0.489, with the total being -8.089. Thus, linkage between panic disorder/agoraphobia and the GABAA beta 1 locus in these pedigrees is exceedingly unlikely.