Statistical Genetic Methods for Cancer Gene Studies

癌症基因研究的统计遗传学方法

• 批准号: 7093535
• 负责人: Susan L Slager
• 金额: $ 11.64万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7093535
• 关键词: clinical research; computer human interaction; computer program /software; computer system design /evaluation; data collection; experimental designs; family genetics; gene environment interaction; human data; mathematical model; method development; model design /development; molecular biology information system; neoplasm /cancer epidemiology; neoplasm /cancer genetics; statistics /biometry

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.

描述（由申请人提供）：找到 常见的复杂疾病是一项艰巨的任务，因为许多遗传和 环境因素是单独或结合的，都会影响特征 表达。使用协会研究应对这一挑战的是 变得更加普遍，尤其是随着人类基因组的释放 顺序。但是，具有足够权力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 联想研究始终被证明不如 病例对照研究，但病例对照研究没有有效地使用数据 收集用于连锁研究和国家注册机构。因此，整体 该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 上述两个设计的组合。具体来说，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有用的信息 主题。 （2）得出并评估用于我们提出的杂种的统计方法 设计。我们将考虑进行分层分析的方法，以匹配 设计，用于DNA聚合以及用于测试相互作用效应。 （3）开发和检查正确人口的统计方法 分层，因为我们提出的设计可能容易受到影响 人口分层。 （4）开发可用于设计的用户友好软件和 分析我们提出的混合设计。 此外，通过计划进行的教学培训，包括 统计遗传学和分子生物学，该指导的建议将 为我提供了建立坚实基础的机会 涉及癌症遗传研究的方法论研究。

项目成果

Genome-wide linkage analysis of systolic blood pressure: a comparison of two approaches to phenotype definition.

收缩压的全基因组连锁分析：两种表型定义方法的比较。

• DOI: 10.1186/1471-2156-4-s1-s13
• 发表时间: 2003
• 期刊: BMC genetics [electronic resource].
• 作者: Slager,SusanL;Iturria,StephenJ
• 通讯作者: Iturria,StephenJ

Identification of genes involved in alcohol consumption and cigarettes smoking.

• DOI: 10.1186/1471-2156-6-s1-s112
• 发表时间: 2005-12-30
• 期刊: BMC GENETICS
• 影响因子: 2.9
• 作者: de Andrade, M;Olswold, CL;Slusser, JP;Tordsen, LA;Atkinson, EJ;Rabe, KG;Slager, SL
• 通讯作者: Slager, SL

Comparison of tagging single-nucleotide polymorphism methods in association analyses.

关联分析中标记单核苷酸多态性方法的比较。

• DOI: 10.1186/1753-6561-1-s1-s6
• 发表时间: 2007
• 期刊: BMC proceedings
• 作者: Goode,EllenL;Fridley,BrookeL;Sun,Zhifu;Atkinson,ElizabethJ;Nord,AlexS;McDonnell,ShannonK;Jarvik,GailP;deAndrade,Mariza;Slager,SusanL
• 通讯作者: Slager,SusanL

Variants in PDE11A and PDE1A are not associated with citalopram response.

PDE11A 和 PDE1A 的变异与西酞普兰反应无关。

• DOI: 10.1038/sj.mp.4002074
• 发表时间: 2007
• 期刊: Molecular psychiatry
• 影响因子: 11
• 作者: Teranishi,KS;Slager,SL;Garriock,H;Kraft,JB;Peters,EJ;Reinalda,MS;Jenkins,GD;McGrath,PJ;Hamilton,SP
• 通讯作者: Hamilton,SP

Pharmacokinetic genes do not influence response or tolerance to citalopram in the STAR*D sample.

• DOI: 10.1371/journal.pone.0001872
• 发表时间: 2008-04-02
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Peters EJ;Slager SL;Kraft JB;Jenkins GD;Reinalda MS;McGrath PJ;Hamilton SP
• 通讯作者: Hamilton SP