Statistical Genetic Methods for Cancer Gene Studies

描述（由申请人提供）：寻找 常见的复杂疾病是一项艰巨的任务，因为许多遗传和 环境因素，无论是单独或组合，影响性状 表情使用关联研究来应对这一挑战是 特别是随着人类基因组的公布， 顺序然而，具有足够力量的大规模关联研究将 需要找到这些具有适度效应大小的基因。基于家庭 关联研究一直被证明不如 病例对照研究，但病例对照研究没有有效地利用数据 为联系研究和国家登记册收集数据。因此整体 本指导建议的目标是开发和调查新的研究 关联研究的设计和统计分析方法， 上述两种设计的组合。具体而言，我们将： (1)检查我们提出的混合设计的采样策略，以便 提供指导方针，使研究人员能够选择最翔实的 科目 (2)推导和评估统计方法用于我们提出的混合 设计我们将考虑分层分析的方法， 设计，用于DNA汇集和用于测试相互作用效应。 (3)开发和检查统计方法，以纠正人口 分层，因为我们提出的设计可能容易受到影响， 人口分层。 (4)开发用户友好的软件，可用于设计和 分析我们提出的混合设计。 此外，通过计划在以下领域开展教学培训， 统计遗传学和分子生物学，这指导建议将 为我提供了一个建立坚实基础的机会， 从事方法学研究的职业，涉及癌症的遗传学研究。

DESCRIPTION (provided by applicant): Finding the genetic determinants of common complex disorders is a formidable task, since many genetic and environmental factors, either individually or in combination, influence trait expression. The use of association studies to tackle this challenge is becoming more widespread, especially with the release of the human genome sequence. However, large-scale association studies with sufficient power will be required to find these genes with modest effect sizes. Family-based association studies have consistently been shown to be less powerful than case-control studies, but case-control studies do not efficiently use the data collected for linkage studies and national registries. Therefore, the overall goal of this mentored proposal is to develop and investigate novel study designs and statistical analysis methods for association studies that are a combination of the two aforementioned designs. Specifically, we will: (1) examine sampling strategies for our proposed hybrid design in order to provide guidelines that enable researchers to choose the most informative subjects. (2) derive and evaluate statistical methods to be used for our proposed hybrid design. We will consider methods for stratified analyses, for matched designs, for DNA pooling, and for testing interaction effects. (3) develop and examine statistical methods that correct for population stratification, since our proposed designs may be susceptible to the effects of population stratification. (4) develop user-friendly software that can be used for the design and analysis of our proposed hybrid designs. Additionally, through the planned didactic training in areas including statistical genetics and molecular biology, this mentored proposal will provide me the opportunity to build a strong foundation upon which to build career conducting methodological research involving genetic studies of cancer.