A Linkage Study of Panic Disorder and Related Phenotypes

描述(申请人提供)：虽然Logue博士在方法开发和数据分析方面在统计遗传学方面获得了丰富的经验，但这项拨款中提议的工作将为Logue博士提供成为一名独立的精神病学遗传学研究人员所需的经验和培训，特别是在惊恐障碍(PD)的研究方面。助学金的共同导师是瓦尔·谢菲尔德博士(HHMI)和托马斯·瓦辛克博士。Thomas Wassink博士将监督精神疾病诊断方面的培训，其中将包括PD遗传学专家Raymond Crowe博士(爱荷华大学)和Myrna Weissman博士(哥伦比亚大学)的直接培训。两位共同导师将参与一个用于确定人类疾病原因的分子遗传学方法的实践培训项目。此外，Linda Brzustowicz博士(罗格斯大学)和Trudy Burns博士(爱荷华大学)将担任这笔赠款的顾问，并将分别在分子遗传学和基因研究设计领域提供额外培训。研究计划包括四个步骤。首先，洛格博士将收集对哥伦比亚基因组筛选数据和爱荷华州连锁研究数据进行联合连锁分析所需的所有信息。这将是迄今为止对帕金森病家系进行的最大规模的联合连锁分析。其次，Logue博士将重新联系爱荷华州联动研究的成员，以便从他们那里获得更多的病史信息，以便根据更大的“综合征”表型对爱荷华州和哥伦比亚大学的数据进行联合分析，该表型暂时被确定为间质性膀胱炎，包括PD、膀胱或肾脏问题、二尖瓣脱垂、头痛和甲状腺问题。第三，使用所有这些数据和表型信息，我们将执行精细图谱基因分型，并缩小感兴趣的间隔。最后，我们将确定至少五个候选基因，我们将检查IA家系中可能导致SNPs的基因。即使帕金森病基因的发现不会立即产生新的治疗选择，基因检测选项的增加也将对公共卫生产生真正的影响，无论是在治疗费用方面(未确诊的帕金森病患者往往是急救服务的高得不成比例的使用者)，还是在目前未被诊断并接受适当治疗的个人的痛苦方面。此外，描绘与帕金森病伴发的共病生理障碍可能会在发现和治疗这些严重疾病的方式上产生进展。

DESCRIPTION (provided by applicant): 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.