The Epilepsy Phenome/ Genome Project (EPGP)

描述（由申请人提供）：癫痫是最常见的神经系统疾病之一，对个人和家庭都有巨大的医疗和社会影响。癫痫治疗方法的开发在很大程度上是经验性的，而不是基于对基本机制的了解，因为人们对癫痫发作和癫痫发生的机制知之甚少。癫痫表型/基因组计划（EPGP）是一项大规模、全国性、多机构合作研究项目，旨在促进我们对最常见的特发性和隐源性癫痫以及症状性癫痫子集的遗传基础的理解；例如，癫痫可能与遗传易感性或发育异常有关，而不是内源性获得性因素，如中枢神经系统感染、头部创伤或中风。EPGP的总体策略是收集3750名癫痫患者和3000名对照组的详细、高质量的表型信息，并使用最先进的基因组和计算方法来确定遗传变异对以下方面的贡献：1)癫痫表型，2)大脑发育异常，以及3)aed治疗患者的不同治疗反应。EPGP联盟成立于3年前，由15个美国学术机构组成，分为行政和科学核心。通过一项计划拨款的资助，该联盟已经规划了登记协议、数据收集方法、分析方法以及开展拟议研究所需的许多基础设施。强大的高通量方法的应用将使我们能够有效地执行大规模基因分型和本应用程序中描述的其他分析。这些研究将使我们能够解决尚未解决的关键问题，这些问题涉及最常见癫痫形式背后的潜在基因组机制，这些机制知之甚少，并促进我们对可变药物反应的遗传学理解。通过NINDS人类遗传信息库及时共享数据和建立患者细胞系将极大地促进全国其他癫痫研究人员的工作。重要的是，EPGP直接符合《癫痫研究基准》基准B2中规定的NINDS高优先级战略目标之一：“组织一个国家科学家小组，通过开展一个将癫痫患者与特定基因模式联系起来的大型筛查项目，共同寻找可能导致癫痫的基因。”

DESCRIPTION (provided by applicant): Epilepsy is one of the most common neurological disorders and has enormous impact, both medical and social, for the individual as well as for the family. Treatments developed for epilepsy have largely been empirical rather than derived from knowledge of basic mechanisms, because the mechanisms underlying seizure occurrence and epileptogenesis are poorly understood. The Epilepsy Phenome/Genome Project (EPGP) is a large-scale, national, multi-institutional, collaborative research project aimed at advancing our understanding of the genetic basis of the most common forms of idiopathic and cryptogenic epilepsies and a subset of symptomatic epilepsy; i.e. epilepsies that are probably related to genetic predispositions or developmental anomalies rather than endogenous, acquired factors such as CNS infection, head trauma or stroke. The overall strategy of EPGP is to collect detailed, high quality phenotypic information on 3,750 epilepsy patients and 3,000 controls, and to use state-of-the-art genomic and computational methods to identify the contribution of genetic variation to: 1) the epilepsy phenotype, 2) developmental anomalies of the brain, and 3) the varied therapeutic response of patients treated with AEDs. The EPGP Consortium was formed 3 years ago and is comprised of 15 U.S. academic institutions and organized into administrative and scientific cores. Through funding from a planning grant, the Consortium has already planned enrollment protocols, data collection methods, analytical approaches, and much of the infrastructure necessary for carrying out the proposed studies. The application of powerful high-throughput methodologies will permit us to efficiently perform the large- scale genotyping and other analyses described in this application. These studies will allow us to address critical unresolved questions concerning the underlying genomic mechanisms behind the most common forms of epilepsy, which are poorly understood, and to advance our understanding of the genetics of variable drug response. Timely data-sharing and the establishment of patient cell lines through the NINDS Human Genetics Repository will greatly facilitate the work of other epilepsy investigators throughout the country. Importantly, EPGP directly matches one of the high-priority, strategic objectives of NINDS as specified in Benchmark B2 of the Benchmarks for Epilepsy Research: "Organize a national group of scientists to work together in search of genes that might contribute to epilepsy by doing a large screening project that links people with epilepsy to particular gene patterns."