Statistical Methods For Gene/environment Interaction And

该项目旨在开发新的统计工具，用于评估基因-环境相互作用和遗传易感性，并将现有的统计工具应用于基因-环境研究的分析。在改进研究设计和相关数据分析技术方面，方法学方面的工作已经展开。在过去一年中，工作主要集中在分析各种研究的数据。 遗传学家使用病例-父母三联体设计来创建一个“理想的”遗传控制组，用于研究变异等位基因与疾病之间的连锁/关联。如果研究者不知道，一个群体由不同的亚群组成，这些亚群具有不同的基因频率和不同的基线疾病风险，那么基因和疾病之间的关联仅仅是由于群体结构而产生的，而不是通过基因和疾病之间的任何因果关系。通过巧妙地创造一个假兄弟姐妹，其基因组成由父母中存在的等位基因组成，但不会传递给病例，遗传学家能够消除人口结构对与变异等位基因相关的风险推断的影响。病例-父母三联设计在应对未知群体结构方面的优势促使我们调查使用这些设计来评估基因型与暴露的相互作用。我们正在继续研究增加病例父母三联体与对照父母三联体的设计，以克服单独使用病例父母三联体的一些缺点。这样的设计应该更充分地将针对人口结构的保护扩展到基因型和暴露的研究。我们也在研究从同一个或不同的黑社会中收集DNA样本的效用，以降低成本，并在提取几乎所有可用信息的同时保留有限的样本。 我们还参与了SOD 2和NQO 1多态性对膀胱癌风险影响的研究数据分析。我们还致力于评估碱基切除修复途径中某些基因的不同单倍型是否与通过单细胞电泳（彗星试验）在培养细胞中测量的表型DNA修复率相关。

This project seeks to develop new statistical tools for evaluating gene-environment interactions and genetic susceptibility and to apply existing statistical tools in the analysis of gene-environment studies. Methodological work has proceeded in the area of improving study designs and associated techniques for data analysis. In the past year, work has largely focused on the analysis of data from a variety of studies. Geneticists use case-parents triad designs to create an "ideal" genetic control group for studying linkage/association between variant alleles and disease. If, unbeknownst to the investigator, a population consists of distinct subpopulations with differing gene frequencies and differing baseline disease risks, associations between gene and disease arise simply by virtue of the population structure, not through any causal connection between the gene and the disease. By cleverly creating a pseudo-sibling whose genetic makeup consists of those alleles present in the parents but not transmitted to the case, geneticists are able to eliminate the effects of population structure on inferences about the risk associated with variant alleles. The advantages of case-parents triad designs in coping with unknown population structure prompted our investigation of using those designs to assess genotype-by-exposure interaction. We are continuing to investigate designs that augment case-parents triads with control-parent triads to overcome some shortcomings of using case-parents triads alone. Such designs should more fully extend protection against population structure to studies of genotype and exposure together. We are also investigating the utility of pooling DNA samples from individuals in the same or different triads to reduce cost and preserve limited samples while extracting nearly all the information available. We have also contributed to the analysis of data from studies on the effects of polymorphisms in SOD2 and NQO1 on bladder cancer risk. We have also worked on assessing whether different haplotypes of certain genes in the Base Excision Repair pathway are associated with phenotypic DNA repair rates measured in cultured cells via single cell electrophoresis (Comet Assay).