Statistical tests for detection of misspecified relationships by use of genome-screen data
Statistical tests for detection of misspecified relationships by use of genome-screen data
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DOI：
10.1086/302800
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发表时间：
2000-03-01
影响因子：
9.8
通讯作者：
Sun, L
中科院分区：
文献类型：
--
作者：
McPeek, MS;Sun, L
不明确的关系可能会对连锁研究产生严重后果，导致连锁研究的有效性降低或假阳性证据。如果系谱中的某些个体是未分型的，则可能不会观察到孟德尔错误。以前通过使用基因型数据来检测错误指定关系的方法仅仅是针对sib和半sib对开发的。我们将gooring和Ott以及Boehnke和Cox的似然计算扩展到更一般的相对对，其中血统身份（IBD）状态不再是马尔可夫链，并且我提出了似然比检验。我们还将Ehm和Wagner的基于状态身份（IBS）的检验扩展到非亲属对。似然比检验具有很高的功效，但它的缺点包括需要为每个可能的替代关系构建和应用单独的马尔可夫链，并且需要模拟来评估显著性。基于ibs的测试更简单，但功耗更低。我们提出了两种新的测试统计-条件预期IBD （EIBD）和调整ibbs (AIBS)-旨在保留IBS的简便性，同时通过考虑机会共享来增加功率。在模拟中，EIBD的功率一般接近似然比检验的功率。在所有病例中，AIBS的威力都高于IBS。我们建议通过使用EIBD和AIBS进行初步筛选，然后仅对使用EIBD和AIBS确定的相对配对的子集应用似然比检验。我们将这些方法应用于来自酒精中毒遗传学合作研究的遗传分析研讨会11数据集。
Misspecified relationships can have serious consequences for linkage studies, resulting in either reduced power or false-positive evidence for linkage. If some individuals in the pedigree are untyped, then Mendelian errors may not be observed. Previous approaches to detection of misspecified relationships by use of genotype data mere developed for sib and half-sib pairs. We extend the likelihood calculations of Goring and Ott and Boehnke and Cox to more-general relative pairs, for which identity-by-descent (IBD) status is no longer a Markov chain, and me propose a likelihood-ratio test. We also extend the identity-by-state (IBS)-based test of Ehm and Wagner to nonsib relative pairs. The Likelihood-ratio test has high power, but its drawbacks include the need to construct and apply a separate Markov chain for each possible alternative relationship and the need for simulation to assess significance. The IBS-based test is simpler but has lower power. We propose two new test Statistics-conditional expected IBD (EIBD) and adjusted IBS (AIBS)-designed to retain the simplicity of IBS while increasing power by taking into account chance sharing. In simulations, the power of EIBD is generally close to that of the likelihood-ratio test. The power of AIBS is higher than that of IBS, in all cases considered. We suggest a strategy of initial screening by use of EIBD and AIBS, followed by application of the likelihood-ratio test to only a subset of relative pairs, identified by use of EIBD and AIBS. We apply the methods to a Genetic Analysis Workshop 11 data set from the Collaborative Study on the Genetics of Alcoholism.