1. Evidence for linkage and association of GABRB3 and GABRA5 to panic disorder.
- Author
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Hodges LM, Fyer AJ, Weissman MM, Logue MW, Haghighi F, Evgrafov O, Rotondo A, Knowles JA, and Hamilton SP
- Subjects
- Alleles, Cell Line, Family, Gene Expression, Genetic Association Studies, Genetic Linkage, Genetic Predisposition to Disease, Genotyping Techniques, Humans, Italy, Lymphocytes metabolism, Microsatellite Repeats, Mutation, Polymorphism, Single Nucleotide, Receptors, GABA-A metabolism, United States, White People genetics, Panic Disorder genetics, Receptors, GABA-A genetics
- Abstract
Panic disorder (PD) is a debilitating anxiety disorder characterized by episodes of intense fear with autonomic and psychological symptoms that lead to behavioral impairment. A convergence of genetic and biological evidence implicates gamma-aminobutyric acid type A receptor subunits on chromosome 15q12 as candidate genes for PD. This study investigated 120 Caucasian, multiplex PD pedigrees using regional microsatellites (chr15q11-13) and found support for linkage (logarithm of odds (LOD) ⩾2), with a prominent parent-of-origin effect. Genotyping with 10 single-nucleotide polymorphisms (SNPs) showed linkage to GABRB3 (rs11631421, LOD=4.6) and GABRA5 (rs2075716, LOD=2.2), and allelic association to GABRB3 (rs8024564, p=0.005; rs8025575, p=0.02) and GABRA5 (rs35399885, p=0.05). Genotyping of an independent Sardinian PD trio sample also supported association in the region, again with a parent-of-origin effect. These findings provide genetic evidence for the involvement of the genes GABRB3 and GABRA5 in the susceptibility to PD.
- Published
- 2014
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