A Linkage Study of Panic Disorder and Related Phenotypes

虽然Logue博士在统计遗传学方面获得了丰富的经验，无论是在方法开发和数据分析方面，这项资助中提出的工作将为Logue博士提供他成为独立精神病遗传学研究人员所需的经验和培训，特别是在惊恐障碍（PD）的研究中。赠款的共同导师是瓦尔谢菲尔德博士（HHMI）和托马斯沃辛克博士。托马斯瓦辛克博士将监督精神疾病诊断方面的培训，其中包括PD遗传学专家雷蒙德·克劳博士（爱荷华州大学）和梅娜·韦斯曼博士（哥伦比亚大学）的直接培训。两位共同导师将参与一个动手训练的程序，用于识别人类疾病的原因分子遗传学方法。此外，琳达Brzustowicz博士（罗格斯大学）和Trudy Burns博士（爱荷华州大学）将担任该基金的顾问，并将分别在分子遗传学和遗传研究设计领域提供额外的培训。研究计划包括四个步骤。首先，罗格博士将收集所有必要的信息，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。这将是迄今为止最大的PD家系联合连锁分析。其次，Logue博士将重新联系爱荷华州连锁研究的成员，以从他们那里获得额外的病史信息，以促进基于更大的“综合征”表型对爱荷华州和哥伦比亚数据的联合分析，暂时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，利用所有这些数据和表型信息，我们将进行精细图谱基因分型，并缩小感兴趣的区间。最后，我们将确定至少五个候选基因，我们将检查可能的因果单核苷酸多态性在IA家系。即使PD疾病基因的发现不会立即产生新的治疗选择，增加的基因检测选择将对公共卫生产生真实的影响，无论是在治疗费用方面（未确诊的PD患者往往是急诊服务的高用户），还是在目前未确诊和接受适当治疗的个人的痛苦方面。此外，伴随PD的共病身体疾病的描述可能会在检测和治疗这些严重疾病的方式上取得进展。

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.