A Research Project in Genetic Epidemiology

遗传流行病学研究项目

基本信息

批准号：
7485770
负责人：
DABEERU C RAO
金额：
$ 26.11万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1980
资助国家：
美国
起止时间：
1980-06-01 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7485770
关键词：
Accounting Address Advertising Architecture Area Attention Brain Bypass Candidate Disease Gene Complex Computer software Computers Data Data Set Detection Development Disease Dissection Educational workshop Environment Epidemiologist Evaluation Face Facility Construction Funding Category Family Fertilization Genes Genetic Genotype Goals Hand Haplotypes Heterogeneity Internet Investigation Linkage Disequilibrium Longevity Maps Methodology Methods Modeling Numbers Parents Participant Performance Phenotype Population Heterogeneity Purpose Research Research Design Research Personnel Research Project Grants Resolution Role Scanning Schedule Series Site Staging Statistical Methods Structure Techniques Testing Trees age related day disease phenotype experience gene environment interaction genetic analysis genetic association genetic epidemiology genetic linkage genetic linkage analysis genome-wide linkage imprint improved innovation interest novel novel strategies programs simulation software development trait trend

项目摘要

DESCRIPTION (provided by applicant): An investigation of the genetic and environmental architecture of complex phenotypes, through an evaluation of a series of hypotheses pertaining to the interrelationships among the variables, constitutes the long-term goal of this (re-revised) proposal. This involves the development and evaluation of novel methods for evaluating the underlying hypotheses. Towards this end, the specific aims cover methodological issues in linkage and association analysis, dense SNP scans and haplotype methods, novel methods for taking advantage of gene-gene (GxG) and gene-environment (GxE) interactions, and novel sequential methods for bypassing the issue of multiple comparisons. Summer workshops will be held which include presentations on the methods and "products" we develop(ed), hands-on computer lab sessions on the use of the products, and brain-storming sessions on the merits and pitfalls of these and other methods/products. All software developed will be freely distributed. The proposed research includes the development and evaluation of statistical methods for the analysis of phenotypic and genotypic data: timely and promising extensions of the variance components linkage models in SEGPATH to incorporate temporal trends in linkage analysis (to capture age-dependent genetic effects), parent-of-origin and imprinting effects, and LD and TDT-like methods; an assessment of the promise of dense SNP scans in candidate genes along with the analysts issues associated with them, theoretical challenges posed by the construction of haplotype maps, ambiguity of block boundaries arising on account of the ambiguity about the makeup of haplotype blocks, and the role of HapMap in mapping complex disease genes; novel methods for finding genes in the presence of GxG and GxE interactions in terms of "tree linkage"; and novel sequential methods for analysis of genome-wide linkage scans and association scans, with particular emphasis on tight control of false positives. Our direct access to several large collaborative family data sets, which have been phenotypically and genotypically well characterized, offers ample opportunity for testing the real utility of these methods. We believe that the proposed research will make a significant contribution to genetic epidemiology.

描述（由申请人提供）：通过评估一系列与变量之间相互关系相关的假设，对复杂表型的遗传和环境结构进行调查，构成了本（重新修订）提案的长期目标。这涉及开发和评估用于评估基本假设的新方法。为此，具体目标涵盖连锁和关联分析、密集 SNP 扫描和单倍型方法、利用基因-基因 (GxG) 和基因-环境 (GxE) 相互作用的新方法以及绕过的新顺序方法中的方法学问题。多重比较的问题。将举办夏季研讨会，其中包括介绍我们开发的方法和“产品”、有关产品使用的计算机实验室实践课程，以及关于这些方法和其他方法的优点和缺陷的头脑风暴会议。产品。所有开发的软件都将免费分发。拟议的研究包括开发和评估用于分析表型和基因型数据的统计方法：及时且有前景地扩展SEGPATH中的方差分量连锁模型，以将时间趋势纳入连锁分析（以捕获年龄依赖性遗传效应），亲本-原点效应和印记效应，以及类似 LD 和 TDT 的方法；对候选基因中密集 SNP 扫描的前景以及与之相关的分析人员问题的评估、单倍型图谱构建带来的理论挑战、由于单倍型块的构成的模糊性而产生的块边界的模糊性以及HapMap 在绘制复杂疾病基因图谱中的作用；在存在 GxG 和 GxE 相互作用的情况下以“树连锁”方式寻找基因的新方法；用于分析全基因组连锁扫描和关联扫描的新颖序贯方法，特别强调严格控制假阳性。我们直接访问几个大型协作家庭数据集，这些数据集已在表型和基因型上得到了很好的表征，为测试这些方法的实际效用提供了充足的机会。我们相信，拟议的研究将对遗传流行病学做出重大贡献。