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，帕金森病 (PD) 就影响了超过一百万人。 PD 是一种复杂的疾病，遗传和环境因素都会导致易感性。剖析帕金森病等复杂疾病的病因需要整合许多不同的实验室和统计方法。该项目寻求继续资助寻找导致特发性帕金森病的基因。认识到PD病因的复杂性以及揭示复杂疾病相关基因的难度，我们采用了“基因组趋同”的方法。我们依靠遗传连锁研究、表达研究和基于家族的关联分析的证据的融合来产生 PD 易感基因的强有力的候选基因。通过这个提案，我们将继续基于基因组收敛原理来检查候选基因。我们将通过分析复杂的遗传和环境相互作用以及开发减少大家庭样本异质性的方法来加强这些努力。该提案的具体目标是：1）测试与PD相关的生物学候选基因；以及项目II基因表达的基因组收敛和连锁分析所建议的候选基因 2) 测试PD候选基因之间的基因-基因相互作用； 3) 测试候选基因与帕金森病潜在环境危险因素之间的基因-环境相互作用。这种综合分析方法以项目 II 和关联中进行的表达分析为指导 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 中发挥作用的基因。