New segregation analysis of panic disorder

Vieland, Veronica J.; Goodman, Daniel; Chapman, Tim F.; Fyer, Abby J.

doi:10.1002/(sici)1096-8628(19960409)67:2<147::aid-ajmg4>3.0.co;2-p

Cited by 60 publications

(23 citation statements)

References 25 publications

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“…Females (males) who were either phenotypically unknown or unaffected had an assumed penetrance model of 66% (33%) with a phenocopy rate of 14% (7%). The genetic parameters for the analyses are based on the results from our previous segregation analyses (Vieland et al, 1993b(Vieland et al, , 1996. Although these parameters may be crude approximations of the unknown, but true, genetic model for panic disorder, considerable work has shown that the magnitude of the lod score is relatively immune to misspecification of genetic parameters like penetrance or gene frequencies (Hodge et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Evidence for Genetic Linkage Between a Polymorphism in the Adenosine 2A Receptor and Panic Disorder

Hamilton

Slager

León

et al. 2003

Neuropsychopharmacol

138

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Data from clinical and behavioral pharmacological studies have implicated adenosine in anxiety behaviors, while genetic studies have suggested that adenosine receptors may be associated with panic disorder. We have undertaken an analysis of several DNA sequence variations in the adenosine 2A receptor (ADORA2A) in a large sample of panic disorder pedigrees. Individuals from 70 panic disorder pedigrees, and 83 child-parent 'trios', were genotyped at five single-nucleotide polymorphisms (SNPs) in and near the ADORA2A gene and were analyzed for genetic linkage and association. Linkage analysis revealed elevated LOD scores for a silent substitution (1083C/T, SNP-4) in the second coding exon. This SNP has been previously reported to be associated with panic disorder. We observed a maximal heterogeneity LOD score of 2.98 (y ¼ 0) under a recessive genetic model and narrow diagnostic model. Other SNPs showed no evidence for linkage. Association tests were not significant for any of the five ADORA2A SNPs. When SNP haplotypes were assessed in the triads with TRANSMIT, one 3-marker haplotype (SNPs 1, 4, 5) was nominally significantly associated with panic disorder (p ¼ 0.029). Pairwise estimations of linkage disequilibrium between the SNPs showed strong patterns of linkage disequilibrium across the ADORA2A locus. Analyses carried out by broadening the panic disorder phenotype to include agoraphobia continued to support linkage to ADORA2A. Our findings provide evidence for a susceptibility locus for panic disorder, and possibly including agoraphobia, either within the ADORA2A gene or in a nearby region of chromosome 22, and serves as the first successful candidate gene replication study in panic disorder.

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Section: Discussionmentioning

confidence: 99%

Evidence for Genetic Linkage Between a Polymorphism in the Adenosine 2A Receptor and Panic Disorder

Hamilton

Slager

León

et al. 2003

Neuropsychopharmacol

138

View full text Add to dashboard Cite

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“…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). Many genes of small effect may contribute to the disease susceptibility.…”

Section: Introductionmentioning

confidence: 99%

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

Rothe

Koszycki

Bradwejn

et al. 2006

Neuropsychopharmacol

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Genetic as well as clinical data suggest that catechol O-methyltransferase (COMT) is involved in multiple complex psychiatric conditions. Recent studies have described an association between the Val158Met COMT polymorphism and panic disorder. Other recent investigations provide evidence that there are other loci within or nearby the COMT gene that may contribute to the susceptibility to panic disorder. To further evaluate the influence of the Val158Met COMT polymorphism in panic disorder we genotyped this marker in the coding region of the COMT gene and two additional variants (rs737865 and rs165599) in the 5 0 and the 3 0 region, respectively, in two independent Canadian samples: 121 nuclear families, and 89 cases with matched controls. In the nuclear families, significant transmission disequilibrium for the valine allele was observed between the alleles of the Val158Met COMT polymorphism and panic disorder (po0.01). A significant excess of the valine allele was found in analysis of the case-control sample (po0.01). This effect was mainly derived from the subgroup of females. This finding, including the female effect, replicates earlier results in studies of the Val158Met polymorphism in panic disorder. No significant results were found for the other two markers. These results support the hypothesis that the valine allele of the Val158Met COMT polymorphism or a nearby locus is involved in the etiopathogenesis of panic disorder.

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“…5 Recent segregation analyses suggest that recessive and dominant modes of inheritance are equally likely, and that panic disorder is unlikely to have a simple Mendelian inheritance. 6,7 These genetic factors have been the focus of recent work employing genome-wide 8 and candidate gene strategies. [9][10][11][12][13][14] Although the psychobiology of panic disorder is a mystery, several lines of evidence underscore a developing understanding of the pathophysiology.…”

Section: Introductionmentioning

confidence: 99%

No association or linkage between polymorphisms in the genes encoding cholecystokinin and the cholecystokinin B receptor and panic disorder

et al. 2000

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Growing animal data implicate cholecystokinin in the regulation of anxiety, while human clinical research confirms the role of cholecystokinin in the provocation of panic attacks. Antipanic medications suppress the ability of cholecystokinin to induce panic attacks, and may alter the expression of the cholecystokinin gene. Thus, there is increased interest in understanding the molecular genetic component of these observations. Recent association studies using persons with panic disorder described some association between polymorphisms in the genes encoding cholecystokinin and the cholecystokinin B-receptor and panic disorder. In this study, we used a family-based design, employing 596 individuals in 70 panic disorder pedigrees, as well as 77 haplotype relative risk 'triads'. Subjects were genotyped for two polymorphisms: the polymorphic microsatellite marker in the CCK-BR locus using PCR-based genotyping and at a single nucleotide polymorphism in the CCK promoter using a fluorescence polarization detection assay, and the data were analyzed for genetic association and linkage. Employing a variety of diagnostic and genetic models, linkage analysis produced no significant lod scores at either locus. Family-based tests of association, the haplotype-based haplotype relative risk statistic and the transmission disequilibrium test, were likewise nonsignificant. The results reported here provide little support for the role of these polymorphisms in panic disorder. Molecular Psychiatry (2001) 6, 59-65.

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New segregation analysis of panic disorder

Cited by 60 publications

References 25 publications

Evidence for Genetic Linkage Between a Polymorphism in the Adenosine 2A Receptor and Panic Disorder

Evidence for Genetic Linkage Between a Polymorphism in the Adenosine 2A Receptor and Panic Disorder

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

No association or linkage between polymorphisms in the genes encoding cholecystokinin and the cholecystokinin B receptor and panic disorder

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