Validation of clinical assessment tools for population genetic studies of epileps

癫痫群体遗传学研究临床评估工具的验证

• 批准号: 8069153
• 负责人: Lawrence Baum
• 金额: $ 4.7万
• 依托单位: CHINESE UNIVERSITY OF HONG KONG
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2012-12-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8069153
• 关键词: Address; Affect; Antiepileptic Agents; Area; Brain; China; Chinese People; Classification; Clinical; Clinical Assessment Tool; Collaborations; Country; DNA; Data; Developing Countries; Development; Diagnosis; Disease; Drug resistance; Electroencephalography; Employment; Epilepsy; Evaluation; Federal Government; Frequencies; Genetic; Genetic Markers; Genetic Polymorphism; Genetic Population Study; Genetic Research; Genotype; Goals; Gold; Hong Kong; Human Resources; Income; Individual; Investigation; Knowledge; Lead; Life; Logistics; MRI Scans; Magnetic Resonance Imaging; Modeling; Pathogenesis; Patients; Pharmaceutical Preparations; Pharmacotherapy; Phenotype; Pilot Projects; Play; Predisposition; Preventive; Public Health; Questionnaires; Recruitment Activity; Research; Research Infrastructure; Research Personnel; Resources; Role; Rural; Saliva; Sampling; Seizures; Specialist; Syndrome; Taiwan; Technology; Training; Translations; United Kingdom; Validation; Variant; base; cohort; effective therapy; follow-up; genetic association; genetic risk factor; genetic variant; genome wide association study; nervous system disorder; outcome forecast; programs; public health relevance; response; tool; treatment program

DESCRIPTION (provided by applicant): It is increasingly recognized that genetic variants play a significant role in the development of a range of common diseases as well as in the individual response to medications. Identifying genetic risk factors for the development of epilepsy and response to antiepileptic drug therapy can lead to major advances in our understanding of the pathogenesis of epilepsy and of drug resistance, leading to new treatment targets and strategies. However, progress in the research as well as application of findings in epilepsy genetics in developing countries, such as rural China, is hampered by deficiency in accurate diagnosis and phenotyping because of lack of specialist expertise and sophisticated investigation techologies. To overcome this critical research and clinical barrier, this research aims to develop the necessary infrastructure through the development and validation of clinical assessment tools for accurate phenotyping and building genetics research capacity, including research logistics, network and personnel training. The research model developed has the potential to be applied in other low- and middle-income countries, where 80% of the world's 50 million epilepsy patients live. Clinical assessment tools (questionnaires) will be developed for phenotyping of epilepsy, focusing on the classification of various seizure types and epilepsy syndromes which have implications for drug choice and prognosis. To validate the assessment tools, they will be applied by village doctors after training to 600 patients selected from the Chinese government's national epilepsy treatment programs. The validity of the clinical assessment tools in phenotyping will be determined by comparing with the gold standard, comprising of specialist evaluation, electroencephalography recording and magnetic resonance imaging of the brain. To obtain preliminary data in identifying genetic marker loci predictive of increased susceptibility to epilepsy, a buccal smear/saliva sample will be obtained from each patient for DNA extraction and subsequent genotyping. Frequencies of the polymorphisms will be compared between patients and controls. Candidate polymorphisms will be selected from significant variants identified in a genome wide association study being carried out in an independent cohort of Chinese epilepsy patients. PUBLIC HEALTH RELEVANCE: Affecting 50 million people worldwide with 80% living in resource poor countries, epilepsy is the most common neurological disorder and a major global public health issue. Understanding the genetic risk factors predisposing to epilepsy and drug resistance can help doctors find better treatment and potentially preventive therapy, but patients in developing countries are often excluded from such research because of lack of expertise and sophisticated investigation technologies to classify the different types of epilepsy. This research aims to develop the necessary infrastructure for conducting large scale genetics research in rural China through the development and validation of clinical assessment tools for accurate phenotyping and building genetics research capacity, including research logistics, network and personnel training.

描述(由申请人提供)：越来越多的人认识到，基因变异在一系列常见疾病的发展以及个人对药物的反应中发挥着重要作用。识别癫痫发生的遗传危险因素和对抗癫痫药物治疗的反应可以使我们对癫痫的发病机制和耐药性的理解有重大进展，导致新的治疗靶点和策略。然而，在中国等发展中国家，由于缺乏专业知识和成熟的调查技术，在癫痫遗传学研究和应用方面的进展受到了准确诊断和表型鉴定不足的阻碍。为了克服这一关键的研究和临床障碍，这项研究旨在通过开发和验证准确的表型鉴定临床评估工具来发展必要的基础设施，并建设遗传学研究能力，包括研究后勤、网络和人员培训。开发的研究模型有可能应用于其他低收入和中等收入国家，全球5000万癫痫患者中有80%生活在这些国家。将开发癫痫表型的临床评估工具(问卷)，重点放在对药物选择和预后有影响的各种癫痫类型和癫痫综合征的分类上。为了验证评估工具的有效性，乡村医生将对从中国政府国家癫痫治疗项目中挑选出来的600名患者进行培训后应用这些评估工具。临床评估工具在表型鉴定方面的有效性将通过与黄金标准的比较来确定，黄金标准包括专家评估、脑电记录和脑磁共振成像。为了获得初步数据，以确定预测癫痫易感性增加的遗传标记基因座，将从每个患者身上获取口腔涂片/唾液样本，用于DNA提取和随后的基因分型。我们将比较患者和对照组之间的基因多态频率。候选多态将从在中国癫痫患者的独立队列中进行的全基因组关联研究中确定的显著变异中选择。 公共卫生相关性：癫痫影响全球5000万人，其中80%生活在资源贫乏的国家，癫痫是最常见的神经疾病，也是一个重大的全球公共卫生问题。了解易患癫痫和耐药性的遗传风险因素可以帮助医生找到更好的治疗方法和潜在的预防性治疗方法，但发展中国家的患者往往被排除在此类研究之外，因为缺乏对不同类型癫痫进行分类的专业知识和复杂的调查技术。本研究旨在通过开发和验证准确表型的临床评估工具，以及建立遗传学研究能力，包括研究后勤、网络和人员培训，为在农村中国开展大规模遗传学研究建立必要的基础设施。

项目成果

Comparing two classification schemes for seizures and epilepsy in rural China.

• DOI: 10.1111/ene.13857
• 发表时间: 2019-03
• 期刊: European journal of neurology
• 影响因子: 5.1
• 作者: Wang F;Chen Z;Davagnanam I;Hoskote C;Ding D;Wang W;Yang B;Wang Y;Wang T;Li W;Sander JW;Kwan P
• 通讯作者: Kwan P

Prevalence of MRI abnormalities in people with epilepsy in rural China.

中国农村癫痫患者 MRI 异常的患病率。

• DOI: 10.1212/wnl.0000000000010171
• 发表时间: 2020
• 期刊: Neurology
• 影响因子: 9.9
• 作者: Davagnanam,Indran;Chen,Zhibin;Hoskote,Chandrashekar;Ding,Ding;Yang,Bin;Wang,Yingli;Wang,Taiping;Li,Wenling;Duncan,JohnS;Wang,Wenzhi;Sander,JosemirW;Kwan,Patrick
• 通讯作者: Kwan,Patrick