Evolutionary-based association analysis using haplotype data
Evolutionary-based association analysis using haplotype data
复制标题
DOI：
10.1002/gepi.10246
复制
发表时间：
2003-07-01
影响因子：
2.1
通讯作者：
Devlin, B
中科院分区：
文献类型：
--
作者：
Seltman, H;Roeder, K;Devlin, B
关联研究，无论是基于家庭的还是基于人群的，都可以成为检测疾病易感性等位基因的有力手段。为了增加测试的信息量，不同的研究人员提出了针对单倍型的建议。然而，相对于单个基因座上的等位基因而言，单倍型的数量较多，可能会降低力量，因为测试需要额外的自由度。最优策略将把测试集中在特定的单倍型或单倍型组上，就像基于分支的关联分析所做的那样。最先由Templeton等人提出。([1987]Genetics 117：343-351)，这种分析使用单倍型之间的进化关系来产生一组有限的假设检验，并增加这些检验的可解释性。为了更充分地利用单倍型之间的进化关系和样本中包含的信息，我们提出了广义线性模型(GLM)来分析基于家庭和基于人群的研究数据。这些模型充分考虑了单倍型阶段的模糊性，并考虑了协变量。这些模型被编码到一个软件包(基于进化的单倍型分析包，EHAP)中，该软件包还提供各种探索性数据分析。探索性分析，如错误检查、单倍型频率估计和构建分支图的工具，应该有助于实现基于分支的单倍型关联分析。(C)2003年Wiley-Liss，Inc.
Association studies, both family-based and population-based, can be powerful means of detecting disease-liability alleles. To increase the information of the test, various researchers have proposed targeting haplotypes. The larger number of haplotypes, however, relative to alleles at individual loci, could decrease power because of the additional degrees of freedom required for the test. An optimal strategy would focus the test on particular haplotypes or groups of haplotypes, much as is done with cladistic-based association analysis. First suggested by Templeton et al. ([1987] Genetics 117:343-351), such analyses use the evolutionary relationships among haplotypes to produce a limited set of hypothesis tests and to increase the interpretability of these tests. To more fully utilize the information contained in the evolutionary relationships among haplotypes and in the sample, we propose generalized linear models (GLM) for the analysis of data from family-based and population-based studies. These models fully account for haplotype phase ambiguity and allow for covariates. The models are encoded into a software package (the Evolutionary-Based Haplotype Analysis Package, EHAP), which also provides for various kinds of exploratory data analysis. The exploratory analyses, such as error checking, estimation of haplotype frequencies, and tools for building cladograms, should facilitate the implementation of cladistic-based association analysis with haplotypes. (C) 2003 Wiley-Liss, Inc.