Family Based Tests of Association for Complex Diseases

复杂疾病关联的家庭测试

• 批准号: 6826253
• 负责人: NAN MCKENZIE LAIRD
• 金额: $ 32.8万
• 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/6826253
• 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）： 该资助的广泛、长期目标是通过持续开发基于家族的关联测试方法来发现复杂性状背后的基因。这类测试越来越受欢迎，因为它们对群体混合具有鲁棒性，并且在性状和标记之间存在关联的情况下，可以是比传统连锁测试更强大的连锁测试。随着人们越来越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也与日俱增。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中获得多个单核苷酸多态性（SNP）将是可行的；在基于家族的测试中使用多个 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整个基因组中 SNP 的识别和绘图的计划。具体来说，我们计划： 1. 当阶段可能不明确并且父母可能不可用时，开发几种补充测试，以检测由多个紧密连锁标记组成的单倍型与疾病表型之间的关联。 2. 开发基于数量性状和发病时间数据排名的新方法。 3. 开发 FBAT 的精确测试版本，当信息族的数量较小和/或使用较小的 alpha 水平时，该版本将提供更准确的 p 值。 4. 将分析功效计算纳入 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，这是我们文档齐全、用户友好的软件，它为实施基于家族的关联测试 (FBAT) 提供了总体策略。