While Dr. Logue has gained substantial experience in statistical genetics, both in methods development and data analysis, the work proposed in this grant would give Dr. Logue the experience and training that he needs to become an independent psychiatric genetic researcher, particularly in the study of panic disorder (PD). The co-mentors on the grant are Dr. Val Sheffield (HHMI), and Dr. Thomas Wassink. Dr. Thomas Wassink, will oversee training in the diagnosis of psychiatric disorders, which will include direct training from PD genetics experts Dr. Raymond Crowe (University of Iowa) and Dr. Myrna Weissman (Columbia University). Both co-mentors will be involved in a program of hands-on training molecular genetics methods used to identify the causes of human disease. Additionally Dr. Linda Brzustowicz (Rutgers University), and Dr. Trudy Burns (University of Iowa) are serving as advisors on this grant, and will provide additional training in the areas of molecular genetics and genetic study design respectively. The research plan contains four steps. First, Dr. Logue will gather all of the information necessary to perform a combined linkage analysis of the Columbia Genome Screen Data, and the Iowa Linkage Study Data. This will represent the largest joint linkage analysis of PD pedigrees to date. Second, Dr. Logue will re-contact the members of the Iowa Linkage study, in order to obtain additional medical history information from them to facilitate joint analysis of the Iowa and Columbia data on the basis of the larger """"""""syndrome"""""""" phenotype, provisionally identified as interstitial cystitis, which includes PD, bladder or kidney problems, mitral valve prolapse, headaches, and thyroid problems. Third, using all of this data and phenotypic information, we will perform fine-map genotyping, and narrow the intervals of interest. Finally, we will identify at least five candidate genes which we will examine for possibly causal SNPs in the IA pedigrees. Even if PD disease gene discovery does not immediately yield new treatment options, the increased options for genetic testing will have a real public health impact, both in terms of treatment dollars (undiagnosed PD sufferers tend to be disproportionately high users of emergency services) and in terms of suffering for individuals not currently diagnosed and receiving proper treatment. In addition, delineation of the co-morbid physical disorders which accompany PD may yield advances in the way that those serious conditions are detected and treated. ? ? ? ?

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Scientist Development Award - Research & Training (K01)
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Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Desmond, Nancy L
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Boston University
Internal Medicine/Medicine
Schools of Medicine
United States
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Wolf, Erika J; Mitchell, Karen S; Logue, Mark W et al. (2014) The dopamine D3 receptor gene and posttraumatic stress disorder. J Trauma Stress 27:379-87
Hodges, Laura M; Fyer, Abby J; Weissman, Myrna M et al. (2014) Evidence for linkage and association of GABRB3 and GABRA5 to panic disorder. Neuropsychopharmacology 39:2423-31
Logue, Mark W; Solovieff, Nadia; Leussis, Melanie P et al. (2013) The ankyrin-3 gene is associated with posttraumatic stress disorder and externalizing comorbidity. Psychoneuroendocrinology 38:2249-57
Logue, M W; Baldwin, C; Guffanti, G et al. (2013) A genome-wide association study of post-traumatic stress disorder identifies the retinoid-related orphan receptor alpha (RORA) gene as a significant risk locus. Mol Psychiatry 18:937-42
Lyons, Michael J; Genderson, Margo; Grant, Michael D et al. (2013) Gene-environment interaction of ApoE genotype and combat exposure on PTSD. Am J Med Genet B Neuropsychiatr Genet 162B:762-9
Miller, Mark W; Wolf, Erika J; Logue, Mark W et al. (2013) The retinoid-related orphan receptor alpha (RORA) gene and fear-related psychopathology. J Affect Disord 151:702-8
Fyer, Abby J; Costa, Ramiro; Haghighi, Fatemeh et al. (2012) Linkage analysis of alternative anxiety phenotypes in multiply affected panic disorder families. Psychiatr Genet 22:123-9
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; Schu, Matthew; Vardarajan, Badri N et al. (2011) A comprehensive genetic association study of Alzheimer disease in African Americans. Arch Neurol 68:1569-79
Logue, Mark W; Bauver, Sarah R; Kremen, William S et al. (2011) Evidence of overlapping genetic diathesis of panic attacks and gastrointestinal disorders in a sample of male twin pairs. Twin Res Hum Genet 14:16-24

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