Leveraging the HapMap correlation structure in association studies
Leveraging the HapMap correlation structure in association studies
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DOI：
10.1086/513109
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发表时间：
2007-04-01
影响因子：
9.8
通讯作者：
Halperin, Eran
中科院分区：
文献类型：
--
作者：
Zaitlen, Noah;Kang, Hyun Min;Halperin, Eran
最近的高通量基因分型技术，如Affytek 500k阵列和Illumina HumanHap 550微珠芯片，已经降低了关联研究的成本，并能够在全基因组范围内测量病例和对照人群之间的单核苷酸多态性（SNP）等位基因频率差异。关联研究效率的一个关键方面是“间接关联”的概念，其中仅收集SNP的子集作为未收集SNP的代理，利用SNP之间的相关结构。最近，一类新的方法间接关联，多标记方法，已被提出。虽然多标记方法是一个相当大的进步，目前的方法没有充分利用SNPs和它们的多标记代理之间的相关结构。在这篇文章中，我们提出了一种新的多标记间接关联方法，WHAP，这是基于单倍型频率差异的加权和。与传统的间接关联方法相比，我们分析表明，与单标记和多标记测试以及传统的基于单倍型的测试相比，我们的方法在功率方面有相当大的增益。我们的结果得到了HapMap参考面板数据集的经验评估的支持，并且可以下载用于Affytoung 500k和Illumina HumanHap 550芯片的软件实现。
Recent high-throughput genotyping technologies, such as the Affymetrix 500k array and the Illumina HumanHap 550 beadchip, have driven down the costs of association studies and have enabled the measurement of single-nucleotide polymorphism (SNP) allele frequency differences between case and control populations on a genomewide scale. A key aspect in the efficiency of association studies is the notion of "indirect association," where only a subset of SNPs are collected to serve as proxies for the uncollected SNPs, taking advantage of the correlation structure between SNPs. Recently, a new class of methods for indirect association, multimarker methods, has been proposed. Although the multimarker methods are a considerable advancement, current methods do not fully take advantage of the correlation structure between SNPs and their multimarker proxies. In this article, we propose a novel multimarker indirect-association method, WHAP, that is based on a weighted sum of the haplotype frequency differences. In contrast to traditional indirect-association methods, we show analytically that there is a considerable gain in power achieved by our method compared with both single-marker and multimarker tests, as well as traditional haplotype-based tests. Our results are supported by empirical evaluation across the HapMap reference panel data sets, and a software implementation for the Affymetrix 500k and Illumina HumanHap 550 chips is available for download.