Background: Family and twin studies indicate that panic disorder is a genetic disease. These data indicate that the genes could act either independently, by either a dominant or a recessive model, or additively. We will complete a 10 cM exclusion map of panic disorder by the end of the current project period. This will test the hypothesis that a major locus accounts for panic disorder in as many as half of the pedigrees. If a major locus is not identified by us or other groups working on panic disorder, it is unlikely that one locus win account for panic disorder, and greater statistical power will be needed to detect disease genes. Power can be increased by expanding the phenotype, increasing the number of pedigrees, and in making the marker map denser.
The specific aims for the next project period address these needs. Progress: We have collected 23 panic disorder pedigrees with 90 cases of DSM III- R panic disorder. We have typed over 400 DNA markers in these families and obtained lod scores less than -2.00 over 85% of the genome under both dominant and recessive models of inheritance. This work has identified a region on chromosome 7p12 where the maximum lod score reaches 2.76. Studies of candidate genes have found a mutation in a transcription factor 5p 1 site of the CCK gene that is present in 34% of panic disorder patients compared with 16% of population controls. These findings need to be followed up.
Specific Aims : In response to the last review, the principal aim of the next grant period is to create a 10 cM joint exclusion map of panic disorder by combining our pedigrees with those of our collaborators at Columbia University.
Other aims are to create 1 cM maps of all regions of interest in the Iowa pedigrees, add three linkage pedigrees per year, perform CO2 inhalation tests for panic attacks on existing and new pedigrees, and collect sample of subjects with panic disorder for an association study.
|Logue, Mark W; Bauver, Sarah R; Knowles, James A et al. (2012) Multivariate analysis of anxiety disorders yields further evidence of linkage to chromosomes 4q21 and 7p in panic disorder families. Am J Med Genet B Neuropsychiatr Genet 159B:274-80|
|Logue, Mark W; Vieland, Veronica J; Goedken, Rhinda J et al. (2003) Bayesian analysis of a previously published genome screen for panic disorder reveals new and compelling evidence for linkage to chromosome 7. Am J Med Genet B Neuropsychiatr Genet 121B:95-9|
|Crowe, R R; Goedken, R; Samuelson, S et al. (2001) Genomewide survey of panic disorder. Am J Med Genet 105:105-9|
|Goedken, R; Ludington, E; Crowe, R et al. (2000) Drawbacks of GENEHUNTER for larger pedigrees: application to panic disorder. Am J Med Genet 96:781-3|
|Wang, Z; Valdes, J; Noyes, R et al. (1998) Possible association of a cholecystokinin promotor polymorphism (CCK-36CT) with panic disorder. Am J Med Genet 81:228-34|
|Garvey, M J; Crowe, R R; Wang, Z (1998) An association of NAG levels and a mutation of the CCK gene in panic disorder patients. Psychiatry Res 80:149-53|
|Crowe, R R; Wang, Z; Noyes Jr, R et al. (1997) Candidate gene study of eight GABAA receptor subunits in panic disorder. Am J Psychiatry 154:1096-100|
|Kato, T; Wang, Z W; Zoega, T et al. (1996) Missense mutation of the cholecystokinin B receptor gene: lack of association with panic disorder. Am J Med Genet 67:401-5|
|Schmidt, S M; Zoega, T; Crowe, R R (1993) Excluding linkage between panic disorder and the gamma-aminobutyric acid beta 1 receptor locus in five Icelandic pedigrees. Acta Psychiatr Scand 88:225-8|
|Wang, Z W; Crowe, R R; Noyes Jr, R (1992) Adrenergic receptor genes as candidate genes for panic disorder: a linkage study. Am J Psychiatry 149:470-4|
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