Pedigree disequilibrium tests for multilocus haplotypes
Pedigree disequilibrium tests for multilocus haplotypes
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DOI：
10.1002/gepi.10252
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发表时间：
2003-09-01
影响因子：
2.1
通讯作者：
Dudbridge, F
中科院分区：
文献类型：
--
作者：
Dudbridge, F
多位点单倍型的关联检验在连锁不平衡作图和候选基因研究中都有重要意义。对于父母三人组的情况下，我讨论了现有的多位点方法的扩展，包括模糊的单倍型模型的测试区分顺式和反式相位。提出了一种似然比检验，使用期望最大化（E-M）算法来解释单倍型的模糊性。关于人口结构的假设是必要的，但现实情况，包括人口分层，违反假设导致保守的测试。我描述了一个置换过程的零假设的利益，控制违反的假设。对于一般家系，我描述扩展的家系不平衡检验，包括不确定的单倍型。汇总统计量被其在单倍型频率先验分布上的期望值替换。如果先验分布不可用，则可以通过使用E-M算法来估计单倍型频率的空分布来进行有效的测试。类似的方法也适用于数量性状。精确的排列检验在小样本中很难构建，但近似程序在大样本中是合适的，并且可以用于解释多个单倍型和基因座的检验之间的依赖性。(C)2003 Wiley-Liss，Inc.
Association tests of multilocus haplotypes are of interest both in linkage disequilibrium mapping and in candidate gene studies. For case-parent trios, I discuss the extension of existing multilocus methods to include ambiguous haplotypes in tests of models which distinguish between the cis and trans phase. A likelihood-ratio test is proposed, using the expectation-maximization (E-M) algorithm to account for haplotype ambiguities. Assumptions about the population structure are required, but realistic situations, including population stratification, which violate the assumptions lead to conservative tests. I describe a permutation procedure for the null hypothesis of interest, which controls for violation of the assumptions. For general pedigrees, I describe extensions of the pedigree disequilibrium test to include uncertain haplotypes. The summary statistics are replaced by their expected values over prior distributions of haplotype frequencies. If prior distributions are not available, a valid test is possible by using the E-M algorithm to estimate the null distribution of haplotype frequencies. Similar methods are available for quantitative traits. Exact permutation tests are difficult to construct in small samples, but an approximate procedure is appropriate in large samples, and can be used to account for dependencies between tests of multiple haplotypes and loci. (C) 2003 Wiley-Liss, Inc.