Design and Analysis of Multi-Staged Association Studies Using Pooled Genomic DNA

使用混合基因组 DNA 进行多阶段关联研究的设计和分析

• 批准号: 7104769
• 负责人: Dietrich A Stephan
• 金额: $ 37万
• 依托单位: TRANSLATIONAL GENOMICS RESEARCH INST
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-15 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7104769
• 关键词: DNA; Internet; automated data processing; computer program /software; computer system design /evaluation; cooperative study; gene expression; gene mutation; genetic screening; genotype; human data; linkage mapping; microarray technology; quantitative trait loci; single nucleotide polymorphism; statistics /biometry

DESCRIPTION (provided by applicant): The technology to simultaneously genotype hundreds of thousands of single nucleotide polymorphisms (SNPs) in a single assay has only recently been developed and has the potential to revolutionize our ability to identify disease-associated genes in complex diseases. Specifically, high density SNP genotyping opens the possibility for case-control genome-wide association studies whereby SNPs that are evolutionary associated with a complex multigenic disease, and also in close physical proximity to a functional mutation, can be discovered. The major drawback of genome-wide association studies is that they require hundreds to thousands of cases and well matched controls for sufficient powering. This type of study is expected to cost millions of dollars using individual genotyping. The overall goal of this proposal is to develop cost effective design strategies and accompanying analysis tools for genome-wide case-control SNP association studies using pooled genomic DNA. We will develop new analysis tools and design strategies for genome-wide association studies using our unparalleled access to high-density genome-wide SNP genotyping data. Within the past six months, we have conducted genome-wide microarray SNP scans on over 5,000 samples. We are currently an early access site for the Affymetrix 500K Mapping array and have already completed two genome-wide scans on pooled DNA using this platform, verifying a previously known disease locus for Progressive Supranuclear Palsy (PSP) and identifying several new loci. We will have access to datasets from multiple genome-wide association studies on pooled genomic DNA including hypertension, Alzheimer's Disease (AD), autism, bipolar disorder, melanoma, PSP, memory, and diabetes. For AD, we will have access to both pooled and individual genotypes for 500K+ SNPs in 1,000 cases and 1,000 controls. Additionally, we have included funding within this proposal for genome-wide association studies on pooled genomic DNA for samples and diseases as decided by the steering community. In the course of this study, we will deliver web-based content and software tools that: (1) aid in the overall design of genome-wide association studies whereby using pooled genomic DNA is one approach; (2) provide quality control metrics for genotyped samples; and (3) automate analysis of a genome-wide association study data from pooled genomic samples.

描述（由申请人提供）：在一次分析中同时对数十万个单核苷酸多态性（snp）进行基因分型的技术是最近才开发出来的，它有可能彻底改变我们在复杂疾病中识别疾病相关基因的能力。具体来说，高密度SNP基因分型为病例对照全基因组关联研究提供了可能性，由此可以发现与复杂的多基因疾病进化相关的SNP，以及与功能突变密切相关的SNP。全基因组关联研究的主要缺点是，它们需要成百上千的病例和匹配良好的对照来获得足够的能量。这种类型的研究预计将花费数百万美元使用个体基因分型。本提案的总体目标是开发具有成本效益的设计策略和附带的分析工具，用于使用汇集的基因组DNA进行全基因组病例对照SNP关联研究。