Results of a genome-wide genetic screen for panic disorder

Abstract

Panic disorder is characterized by spontaneous and recurrent panic attacks, often accompanied by agoraphobia. The results of family, twin, and segregation studies suggest a genetic role in the etiology of the illness. We have genotyped up to 23 families that have a high density of panic disorder with 540 microsatellite DNA markers in a first-pass genomic screen. The thirteen best families (ELOD > 6.0 under the dominant genetic model) have been genotyped with an ordered set of markers encompassing all the autosomes, at an average marker density of 11 cM. Over 110,000 genotypes have been generated on the whole set of families, and the data have been analyzed under both a dominant and a recessive model, and with the program SIBPAIR. No lod scores exceed 2.0 for either parametric model. Two markers give lod scores over 1.0 under the dominant model (chromosomes 1p and 20p), and four do under the recessive model (7p, 17p, 20q, and X/Y). One of these (20p) may be particularly promising. Analysis with SIBPAIR yielded P values equivalent to a lod score of 1.0 or greater (i.e., P < .016, one-sided, uncorrected for multiple tests) for 11 marker loci (2, 7p, 8p, 8q, 9p, 11q, 12q, 16p, 20p and 20q).

Linkage on chromosome 14 in a genome-wide linkage study of a broad anxiety phenotype

“…[3][4][5] Several genome-wide linkage studies have tried to identify genomic regions harboring quantitative trait loci (QTLs) that influence the vulnerability for anxiety disorders. All these studies [6][7][8][9][10][11][12][13][14][15] ascertained the pedigrees through probands with panic disorder, except for one study 16 that included pedigrees with at least one member having an anxiety disorder or somatoform pain. Panic disorder is the most frequently analyzed phenotype.…”

“…Panic disorder is the most frequently analyzed phenotype. [6][7][8]13,14 Two studies focused on panic disorder with comorbid medical conditions, that is renal/ bladder conditions, thyroid irregularities, mitral valve prolapse and severe headaches. 11,15 Simple phobia and social phobia have each been investigated once.…”

“…Table 1 summarizes the most promising results so far. One region on chromosome 7 and one region on chromosome 1 showed linkage in two scans 6,8,13,14 with logarithm of odds (LOD) scores from 1.71 to 2.23. A linkage signal on chromosome 14 was observed for panic disorder, simple and social phobia in a sample of 20 families with 153 individuals.…”

Association of the Val158Met Catechol O-Methyltransferase Genetic Polymorphism with Panic Disorder

“…Family and twin studies suggest a genetic component in the etiopathogenesis of PD with an estimated heritability of up to 46% (Hettema et al, 2001). In genomewide scans, several possible regions for panic disorder have been identified (Crowe et al, 1987;Gelernter et al, 2001;Hamilton et al, 2003;Knowles et al, 1998;Thorgeirsson et al, 2003), among them one locus on chromosome 11 in the region of the cholecystokinin-B receptor (CCKBR) gene (Gelernter et al, 2001). PD is considered a complex psychiatric disorder as there has been no simple Mendelian pattern of inheritance found in segregation studies (Vieland et al, 1996).…”

Transgenic mice overexpressing the full-length neurotrophin receptor TrkC exhibit increased catecholaminergic neuron density in specific brain areas and increased anxiety-like behavior and panic reaction

“…Recurrent panic attacks define panic disorder, a common and severe anxiety disorder of unknown etiology. Although several chromosomal regions and genes have been suggested to contribute to panic disorder, the phenotypic and genetic complexity of this disorder has precluded the finding of candidate genes (Knowles et al, 1998;Weissman et al, 2000;Crowe et al, 2001;Gratacos et al, 2001; Thorgeirsson et al, 2003). It has been proposed that genetic variants of several candidate genes of neurotransmitter systems, mainly catecholaminergic, may con-tribute to the susceptibility to panic disorder (Maron et al, 2005).…”