Family Based Tests of Association for Complex Diseases

复杂疾病关联的家庭测试

• 批准号: 6577113
• 负责人: NAN MCKENZIE LAIRD
• 金额: $ 36.41万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6577113
• 关键词: clinical research; computer program /software; disease /disorder; family genetics; gene expression; genetic markers; genetic polymorphism; genetic screening; genetic susceptibility; genetic techniques; genotype; human data; method development; phenotype; statistics /biometry

DESCRIPTION (provided by applicant): The broad, long-term objective of this grant is to enable the discovery of genes underlying complex traits by the continued development of methods for family-based association tests. This class of tests has grown in popularity because they are robust to population admixture, and can be more powerful tests of linkage than conventional linkage tests in the presence of association between the trait and the marker. Interest in association strategies is growing with increasing recognition of the limitations of linkage strategies in localizing genes for complex diseases. Moreover, with the near completion of the map of the human genome, it will be feasible to obtain multiple single nucleotide polymorphisms (SNPs) in candidate genes of interest or regions of linkage; using multiple SNPs in family-based tests will provide a powerful strategy for finding disease genes. Initiatives devoted to the identification and mapping of SNP's throughout the genome are currently underway. Specifically, we plan to: 1. Develop several complementary tests for association between haplotypes composed from multiple tightly-linked markers and disease phenotypes when phase may be ambiguous and parents may not be available. 2. Develop new methods based on ranks for quantitative traits and time-to-onset data. 3. Develop an exact-test version of FBAT that will provide more accurate p-values when the number of informative families is small and/or a small alpha-level is used. 4. Incorporate analytic power calculations into FBAT which will enable users to determine the most powerful designs, select appropriate sample sizes and choose the most powerful tests. 5. Continue the development, updating, and maintenance of FBAT, our fully documented, user friendly software which provides a general strategy for implementing Family-Based Tests of Association (FBAT).

描述（由申请人提供）： 这笔赠款的广泛，长期的目标是通过持续开发基于家庭的关联测试方法来发现基因复杂性状的基因。这类测试之所以越来越受欢迎，因为它们对种群混合具有强大的态度，并且在性状与标记之间存在关联的情况下，与常规的链接测试相比，链接的强大测试可能更强大。随着对链接策略在本地化基因的局限性局限性的局限性，对关联策略的兴趣正在增长。此外，随着人类基因组图的近乎完成，可以在感兴趣的候选基因或链接区域获得多个单核苷酸多态性（SNP）是可行的。在基于家庭的测试中使用多个SNP将为寻找疾病基因提供强大的策略。 目前正在进行致力于在整个基因组中识别和映射SNP的倡议。具体来说，我们计划： 1。在相位模棱两可的情况下，开发了由多个紧密连接标记组成的单倍型与疾病表型组成的单倍型之间的互补测试，而父母可能不可用。 2。根据定量性状和发出时间数据的等级制定新方法。 3。开发一个精确的FBAT测试版本，当信息范围的家庭数量较小和/或使用小α级时，该版本将提供更准确的p值。 4。将分析能力计算纳入FBAT，这将使用户能够确定最强大的设计，选择适当的样本尺寸并选择最强大的测试。 5。继续对FBAT的开发，更新和维护，这是我们完全记录的，用户友好的软件，该软件提供了实施基于家庭的协会测试（FBAT）的一般策略。