VARIANCE COMPONENTS MODELS FOR MAPPING QTLS

用于绘制 QTLS 的方差分量模型

• 批准号: 6329577
• 负责人: JOHN K. HEWITT
• 金额: $ 24.43万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-07 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6329577
• 关键词: analytical method; computer data analysis; computer program /software; computer simulation; family genetics; gene environment interaction; gene expression; genetic disorder diagnosis; genotype; human data; human population genetics; linkage disequilibriums; linkage mapping; model design /development; phenotype; quantitative trait loci; statistics /biometry

We propose to develop our work on variance components methods for mapping QTLs for human complex traits using both association and linkage approaches. We will produce documentation for our existing programs for both stimulation and analysis and integrate these into a comprehensive package. We will extend our approach to include the interaction of QTLs with both the environment and with other loci, i.e., genotype X environment interaction and epistasis. We will include recent work on multivariate analysis with a view to increasing statistical power. We will generalize our analytic approach to a limited number of relatives other than sibs. One particularly novel aspect of our proposal is the development of a new test of association involving siblings which controls for population stratification and increases statistical power through the use of siblings selected for extreme scores on a continuous phenotype. This new test will be embedded in a maximum likelihood variance components approach where association will be modeled through sibling means and linkage will be modeled through the covariance matrix. This combined linkage-association test will yield novel information about the genetic architecture of complex traits. The transmission disequilibrium test will be rigorously developed for use with continuous traits either separately or combined with our new sibling test of association. The emphasis in our new proposal is on new approaches involving selected samples and maximum likelihood variance components analysis in order to achieve an integrated approach to mapping genes for complex traits.

我们建议发展我们的工作方差分量的方法定位QTL的人类复杂性状使用关联和连锁的方法。 我们将为我们现有的刺激和分析程序编制文件，并将这些文件整合到一个全面的软件包中。 我们将扩展我们的方法，包括QTL与环境和其他基因座的相互作用，即，基因型X环境互作和上位性。我们将包括最近的工作，多变量分析，以期增加统计权力。 我们将把我们的分析方法推广到非同胞的有限数量的亲属。 我们的建议的一个特别新颖的方面是开发一种新的测试的关联，涉及控制人口分层和增加统计能力，通过使用的兄弟姐妹选择的极端分数的连续表型的兄弟姐妹。 这种新的检验将嵌入最大似然方差分量方法中，其中关联将通过同级均值建模，连锁将通过协方差矩阵建模。 这种联合连锁-关联检验将产生关于复杂性状遗传结构的新信息。 传递不平衡检验将被严格地开发，以单独或与我们新的同胞关联检验相结合地用于连续性状。 在我们的新建议的重点是新的方法，涉及选定的样本和最大似然方差分量分析，以实现一个综合的方法来定位基因的复杂性状。