Genetic Epidemiology of Seizure Disorders In Rochester

描述（由申请人提供）：已取得实质性进展 最近在癫痫易感基因的位置克隆中， 孟德尔式传播的家庭。然而，人们对 遗传对不同癫痫综合征的影响程度， 人群，或由特定遗传因素产生的临床表型的范围 机制等我们建议在基于人群的研究中解决这些问题 对特定癫痫发作疾病的共同和独特的遗传影响， 癫痫综合征，使用罗切斯特-奥姆斯特德县记录的数据 联系项目。病例先证者将是1920年出生的所有罗切斯特居民，或 后来发生癫痫或孤立的无端癫痫发作， 1935-1994年（N=1056）。对照先证者将是没有无缘无故 癫痫发作，按出生年份、种族和 罗切斯特的住院医师。诊断和分类将基于对 医疗记录，辅以半结构化诊断访谈，以确保 系统地收集基本临床特征的数据。 病例一级亲属中癫痫发作疾病的信息， 对照将通过审查亲属的医疗记录来收集， 并辅以先证者访谈。血液样本将收集从生活 用于候选基因关联研究的病例和对照。数据将 用于评估癫痫的哪些临床特征最有可能预测 遗传易感性是否遗传对癫痫的影响也升高 其他癫痫疾病的风险（孤立的无端癫痫发作，发热性 惊厥和其他急性症状性癫痫发作），以及是否不同 临床定义的癫痫综合征具有共同或不同的遗传 影响。女性和男性的后代中癫痫发作疾病的风险 将先证者进行比较，以探索先前观察到的母体效应， 癫痫一组候选基因编码电压门控或 配体门控离子通道将在直接和间接研究 利用单核苷酸的（单倍型或基于标记的）关联测试 多态性（SNP）。

DESCRIPTION (provided by applicant): Substantial progress has been made recently in positional cloning of epilepsy susceptibility genes in unusual families with Mendelian forms of transmission. However, little is known about the magnitude of genetic effects on different epilepsy syndromes in the population, or the range of clinical phenotypes produced by specific genetic mechanisms. We propose to address these questions in a population-based study of the shared and distinct genetic influences on specific seizure disorders and epilepsy syndromes, using data from the Rochester-Olmsted County Records Linkage Project. Case probands will be all Rochester residents born in 1920 or later with incidence of epilepsy or an isolated unprovoked seizure from 1935-1994 (N=1056). Control probands will be individuals without unprovoked seizures, matched to the cases by birth year, ethnicity, and length of Rochester residency. Diagnosis and classification will be based on review of medical records, supplemented by semistructured diagnostic interviews to ensure that data are collected systematically on essential clinical features. Information on seizure disorders in the first-degree relatives of cases and controls will be collected by review of the medical records of the relatives, supplemented by proband interviews. Blood samples will be collected from living cases and controls for candidate gene association studies. The data will be used to assess which clinical features of epilepsy are most likely to predict a genetic susceptibility whether the genetic influences on epilepsy also raise risk for other seizure disorders (isolated unprovoked seizures, febrile convulsions, and other acute symptomatic seizures), and whether different clinically-defined epilepsy syndromes have shared or distinct genetic influences. Risks of seizure disorders in the offspring of female and male probands will be compared to explore the previously observed maternal effect in epilepsy. A set of candidate genes encoding either voltage-gated or ligand-gated ion channels will be investigated in both direct and indirect (haplotype or marker-based) association tests utilizing single nucleotide polymorphisms (SNPs).