2014 Articles

Evidence For Linkage And Association Of Gabrb3 And Gabra5 To Panic Disorder

Hodges, Laura M; Fyer, Abby J.; Weissman, Myrna M.; Logue, Mark W.; Haghighi, Fatemeh; Evgrafov, Oleg; Rotondo, Allessandro; Knowles, James A.; Hamilton, Steven P.

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.