title: Evidence for linkage and association of GABRB3 and GABRA5 to panic disorder.
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.
authors.affiliation: Department of Psychiatry and Institute for Human Genetics, University of California, San Francisco, CA, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Hodges
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York, NY, USA.
authors.forename: Abby J
authors.initials: AJ
authors.lastname: Fyer
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York, NY, USA.
authors.forename: Myrna M
authors.initials: MM
authors.lastname: Weissman
authors.affiliation: Biomedical Genetics, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Logue
authors.affiliation: Department of Psychiatry, Icahn School of Medicine, New York, NY, USA.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Haghighi
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Oleg
authors.initials: O
authors.lastname: Evgrafov
authors.affiliation: Department of Psychiatry, University of Pisa, Pisa, Italy.
authors.forename: Allessandro
authors.initials: A
authors.lastname: Rotondo
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Knowles
authors.affiliation: 1] Department of Psychiatry and Institute for Human Genetics, University of California, San Francisco, CA, USA [2] Department of Psychiatry, Kaiser Permanente Medical Center, San Francisco, CA, USA.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Hamilton
mesh_terms: D000483:Alleles; D002460:Cell Line; D005190:Family; D015870:Gene Expression; D056726:Genetic Association Studies; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006801:Humans; D007558:Italy; D008214:Lymphocytes / Q000378:metabolism; D018895:Microsatellite Repeats; D009154:Mutation; D016584:Panic Disorder / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011963:Receptors, GABA-A / Q000235:genetics* / Q000378:metabolism; D014481:United States; D044465:White People / Q000235:genetics
chemical_list: C527986:GABRA5 protein, human; C546273:GABRB3 protein, human; D011963:Receptors, GABA-A
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