This is an application for a Research Scientist Award to support the applicant's research on the genetics of panic disorder and several other psychiatric conditions. Panic disorder is familial and twin studies indicate that genes are involved in its transmission, but the low relative risk of first-degree relatives suggests that individual loci make small contributions to overall liability. Indeed, we have completed a genome search for linkage with over 400 STRP markers and excluded a major locus from 85% of the genome. Over the next phase of the project we hope to accomplish several objectives. We need to create dense marker maps of the regions that resulted in positive evidence of linkage from the genome search. We will also collect a sample of panic disorder patients for disequilibrium studies. We will combine our pedigrees with those of our collaborators at Columbia University to increase power to detect loci of small effect. Both groups will study 35% CO2 inhalation, a potential biological marker for panic disorder, in their pedigrees in hopes of finding a more valid biological phenotype for linkage analysis. The applicant has identified a mutation in the promoter of the CCK gene, a candidate gene for panic disorder, that may be associated with panic disorder. This association will be studied in an epidemiological sample, and its effect on gene transcription will be studied using a reporter gene construct At the same time, the applicant is participating in collaborative linkage studies of three other disorders. I am the PI of the Iowa site on a six-center collaborative study on the genetics of alcoholism. I have also contributed schizophrenia pedigrees to a collaborative effort to search for genes for that disease. The applicant and PIs at four other sites are planning to submit an application for a linkage study of early-onset unipolar depression. Finally, I am the project director of a postdoctoral fellowship in psychiatric genetics at Iowa that has been continuously funded for over 20 years. All of these projects are time consuming. At the same time, demands on clinical faculty for service time are becoming increasingly pressing as a result of recent changes in the health care environment. The Research Scientist Award will free my time from service requirements to work on the above genetics projects.
