Candidate Genes and Complex Interactions in PD

PD 中的候选基因和复杂的相互作用

• 批准号: 6812934
• 负责人: Eden R. Martin
• 金额: $ 17.67万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6812934
• 关键词: Parkinson' s disease; biotechnology; clinical research; disease /disorder etiology; family genetics; functional /structural genomics; gene environment interaction; gene expression; gene interaction; genetic screening; genetic susceptibility; genotype; human data; human genetic material tag; human subject; linkage disequilibriums; nervous system disorder epidemiology; pathologic process; questionnaires; single nucleotide polymorphism; statistics /biometry

Parkinson disease (PD) affects over one million people in the United States alone. PD is a complex disorder, with both genetic and environmental factors contributing to susceptibility. Dissecting the etiology of complex diseases, such as PD, requires the integration of many different laboratory and statistical approaches. This project seeks to continue funding to search for genes contributing to idiopathic PD. Recognizing the complex etiology of PD and the difficulties in uncovering genes involved in complex diseases, we have adopted the approach of "genomic convergence". We have relied on the convergence of evidence from genetic linkage studies, expression studies and family-based association analysis to yield strong candidates for PD susceptibility genes. Through this proposal, we will continue to examine candidate genes based on the principle of genomic convergence. We will enhance these efforts by including analysis of complex genetic and environmental interactions, as well as developing methods to reduce heterogeneity in our large family sample. The specific aims of this proposal are: 1) Test biological candidate genes for association with PD; and candidates suggested by the genomic convergence of gene expression from project II and linkage analysis 2) Test for gene-gene interaction between candidate genes in PD; and 3) Test for gene-environment interaction between candidate genes and potential environmental risk factors for PD. This comprehensive analytic approach, guided by the expression analysis conducted in Project II and association mapping in Project IV of this proposal, will allow us to systematically evaluate and identify genes playing a role in PD.

仅在美国，帕金森氏病（PD）就会影响100万人。 PD是一种复杂的疾病，遗传和环境因素既导致易感性。解剖复杂疾病（例如PD）的病因需要整合许多不同的实验室和统计方法。该项目试图继续资金，以寻找对特发性PD造成的基因。认识到PD的复杂病因以及发现参与复杂疾病的基因的困难，我们采用了“基因组收敛”的方法。我们依靠遗传联系研究，表达研究和基于家庭的关联分析的证据收敛，以产生PD易感基因的强大候选者。通过该提案，我们将继续根据基因组收敛原理检查候选基因。我们将通过包括对复杂遗传和环境相互作用的分析以及开发减少大型家庭样本异质性的方法来加强这些努力。该提案的具体目的是：1）测试与PD关联的生物候选基因；以及来自项目II和链接分析的基因表达的基因组收敛提示的候选者2）测试PD中候选基因之间的基因 - 基因相互作用； 3）测试候选基因与PD潜在环境风险因素之间的基因环境相互作用。在项目II和关联中进行的表达分析的指导下，这种全面的分析方法 该提案项目IV中的映射将使我们能够系统地评估和识别在PD中起作用的基因。