Genomic screening and replication using the same data set in family-based association testing
Genomic screening and replication using the same data set in family-based association testing
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DOI：
10.1038/ng1582
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发表时间：
2005-07-01
期刊：
影响因子：
30.8
通讯作者：
Lange, C
中科院分区：
文献类型：
--
作者：
Van Steen, K;McQueen, MB;Lange, C
人类基因组计划及其副产品使利用全基因组关联研究来确定复杂特征的遗传基础变得越来越可行。分析这类研究的统计学挑战源于对数千个SNP的分析导致的严重的多重比较问题。我们使用单个SNP或单倍型进行全基因组家庭关联研究的方法，可以识别实现全基因组意义的关联。在为我们的筛查工具制定指南方面，我们确定了检测疾病易感基因的估计能力的下限，无论数据中存在的连锁不平衡结构如何，这一下限都成立。我们还评估了在存在多个疾病易感基因的情况下我们的方法的力量。我们的筛查工具适应基因组控制，并使用单倍型标记SNPs的概念。我们的方法使用整个样本，不需要单独的筛选和验证样本来确定全基因组意义，而基于总体的设计则是这样做的。
The Human Genome Project and its spin- offs are making it increasingly feasible to determine the genetic basis of complex traits using genome- wide association studies. The statistical challenge of analyzing such studies stems from the severe multiple-comparison problem resulting from the analysis of thousands of SNPs. Our methodology for genome- wide family- based association studies, using single SNPs or haplotypes, can identify associations that achieve genome- wide significance. In relation to developing guidelines for our screening tools, we determined lower bounds for the estimated power to detect the gene underlying the disease- susceptibility locus, which hold regardless of the linkage disequilibrium structure present in the data. We also assessed the power of our approach in the presence of multiple disease- susceptibility loci. Our screening tools accommodate genomic control and use the concept of haplotype- tagging SNPs. Our methods use the entire sample and do not require separate screening and validation samples to establish genome- wide significance, as population- based designs do.