A Method for Validating Gene - Disease Associations

验证基因-疾病关联的方法

• 批准号: 6790529
• 负责人: Colin B Begg
• 金额: $ 8.43万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6790529
• 关键词: cancer risk; family genetics; gene environment interaction; gene frequency; genotype; longitudinal human study; neoplasm /cancer epidemiology; statistics /biometry

DESCRIPTION (provided by applicant): The case-control study is being used increasingly to evaluate cancer risks of common genetic variants. It is commonplace for detailed information on family history of disease to be collected in these studies. The rationale for this investigation is the belief that these data on family history are not utilized efficiently by investigators. Data on the family history of first degree relatives can be assembled in a retrospective "kin-cohort", and analyzed using cohort-study methodology, whereby the incident rates of the cancer under study in relatives of gene "carriers" are compared with the rates in relatives of "non-carriers". In this application we show that the rate ratio from a kin-cohort analysis of this nature can be expressed as a function of the rate ratio of interest (i.e. the parameter that is directly estimated in the case-control study). Thus the kin-cohort analysis can be used, in principle, as an independent verification of any genetic associations observed in the case-control study. We present evidence to suggest that the kin-cohort might have good statistical power for this purpose for the study of common cancers. In this application we plan to study in detail the statistical power of the kin-cohort analysis relative to that of the case-control study from which the data for the kin-cohort are derived. We will examine the relative efficiency of the kin-cohort analysis in relation to the underlying incidence rate of the cancer under study, the population frequency and the relative risk of the genotype. The method will also be extended to the study of the joint effect of two genotypes, and the evaluation of haplotypes. It is anticipated that the project will demonstrate that for commonly occurring cancers the kin-cohort analysis can provide an immediate independent confirmation (or refutation) of genetic associations that are observed serendipitously in case-control studies.

描述(由申请人提供)： 病例对照研究越来越多地被用于评估常见基因变异的癌症风险。在这些研究中收集关于家族病史的详细信息是司空见惯的。这项调查的理由是认为这些关于家族史的数据没有被调查人员有效地利用。关于一级亲属的家族史的数据可以收集在一个回溯性的“亲属队列”中，并使用队列研究方法进行分析，从而将基因“携带者”亲属的癌症发病率与“非携带者”亲属的发病率进行比较。在这个应用中，我们证明了来自这种性质的亲属队列分析的利率比率可以表示为利率比率的函数(即在病例对照研究中直接估计的参数)。因此，亲属队列分析原则上可用作病例对照研究中观察到的任何遗传关联的独立验证。我们提出的证据表明，对于常见癌症的研究，亲属队列可能具有很好的统计能力。在这项应用中，我们计划详细研究亲属队列分析相对于病例对照研究的统计能力，从病例对照研究中得出亲属队列的数据。我们将检验亲属队列分析的相对效率与所研究癌症的潜在发病率、人群频率和该基因的相对风险之间的关系。该方法还将扩展到两种基因联合效应的研究和单倍型的评估。预计该项目将证明，对于常见癌症，亲属队列分析可以立即独立地证实(或驳斥)在病例对照研究中偶然观察到的遗传关联。