Family Based Tests of Association for Complex Diseases

复杂疾病关联的家庭测试

• 批准号: 6987843
• 负责人: NAN MCKENZIE LAIRD
• 金额: $ 32.03万
• 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/6987843
• 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)： 这笔赠款的广泛和长期目标是通过继续开发基于家庭的关联测试方法来发现复杂性状的潜在基因。这类测试越来越受欢迎，因为它们对群体混合很健壮，而且在性状和标记之间存在关联的情况下，可以比传统的连锁测试更有效地进行连锁测试。随着人们越来越多地认识到连锁策略在定位复杂疾病基因方面的局限性，人们对关联策略的兴趣与日俱增。此外，随着人类基因组图谱的接近完成，在感兴趣的候选基因或连锁区域获得多个单核苷酸多态(SNPs)将是可行的；在基于家族的测试中使用多个SNPs将为发现疾病基因提供强有力的策略。致力于识别和绘制全基因组SNP的倡议目前正在进行中。具体来说，我们计划： 1.发展了几个互补的检验方法，用于由多个紧密连锁的标记组成的单倍型与疾病表型之间的关联，当阶段可能不明确且亲本可能不可用时。 2.发展基于等级的数量性状和发病时间数据的新方法。 3.开发FBAT的精确测试版本，当信息族数量较少和/或使用较小的Alpha级别时，该版本将提供更准确的p值。 4.将解析功率计算纳入FBAT，这将使用户能够确定最强大的设计，选择合适的样本大小，并选择最强大的测试。 5.继续开发、更新和维护FBAT，这是我们的完整文档、用户友好的软件，为实施基于家庭的关联测试(FBAT)提供了一般策略。