Candidate Genes and Complex Interactions in PD

帕金森氏症（PD）仅在美国就影响了100多万人。PD是一种复杂的疾病，遗传和环境因素都对其易感性有影响。解剖复杂疾病的病因，如帕金森病，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。认识到帕金森病的复杂病因和揭示复杂疾病相关基因的困难，我们采用了“基因组趋同”的方法。我们依靠来自遗传连锁研究、表达研究和基于家庭的关联分析的证据聚合来产生PD易感基因的强有力候选基因。通过这一提议，我们将继续基于基因组趋同的原则来检查候选基因。我们将通过分析复杂的遗传和环境相互作用，以及开发方法来减少我们大家庭样本的异质性来加强这些努力。本课题的具体目的是：1)检测与PD相关的生物学候选基因；2) PD候选基因间的基因互作检验；3)检测PD候选基因与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Project II和association的表达分析为指导

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.