A graphical assessment of p-values from sliding window haplotype tests of association to identify asthma susceptibility loci on chromosome 11q.

A graphical assessment of p-values from sliding window haplotype tests of association to identify asthma susceptibility loci on chromosome 11q.
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DOI:
10.1186/1471-2156-7-38
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发表时间:
2006-06-14
期刊:
影响因子:
2.9
通讯作者:
Huang SK
Huang SK
中科院分区:
生物学3区
文献类型:
--
作者:
Mathias RA;Gao P;Goldstein JL;Wilson AF;Pugh EW;Furbert-Harris P;Dunston GM;Malveaux FJ;Togias A;Barnes KC;Beaty TH;Huang SK

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过去对哮喘非裔美国人家庭的研究显示,11号染色体上有一个强烈的连锁峰,并有适度的证据表明存在关联。在这里,我们使用滑动窗口方法在非裔美国人受试者中进行哮喘和609个SNP的相关性测试。虽然这种方法在筛选基因型密集的区域方面很有效,但确实会产生一些问题:大量的测试、吸收数千个结果,以及在具有关联信号的区域上设置优先级的问题。我们提出了一种新开发的工具,滑动P值的图形评估或GrASP,它使用颜色显示来指示滑动窗口的宽度,单个测试的意义,SNP覆盖的密度和已知基因的位置,简化了其中的一些问题,并使用它来识别这些数据中的感兴趣区域。我们证明了GrASP可以更容易地从滑动窗口单倍型分析中可视化,总结和优先考虑感兴趣的区域,共同基于来自这些窗口的所有测试的p值和该区域中有意义的单倍型的构建。使用这种方法,五个地区产生了强有力的证据与哮喘的联系和关联,包括先前的高峰联系区域。
Past work on asthmatic African American families revealed a strong linkage peak with modest evidence of association on chromosome 11q. Here, we perform tests of association for asthma and a panel of 609 SNPs in African American subjects using a sliding window approach. While efficient in screening a region of dense genotyping, this approach does create some problems: high numbers of tests, assimilating thousands of results, and questions about setting priorities on regions with association signals. We present a newly developed tool, Graphical Assessment of Sliding P-values or GrASP, which uses color display to indicate the width of the sliding windows, significance of individual tests, density of SNP coverage and location of known genes that simplifies some of these issues, and use it to identify regions of interest in these data. We demonstrate that GrASP makes it easier to visualize, summarize and prioritize regions of interest from sliding window haplotype analysis, based jointly on the p-value from all the tests from these windows and the building of haplotypes of significance in the region. Using this approach, five regions yielded strong evidence for linkage and association with asthma, including the prior peak linkage region.
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