Combining identity by descent and association in genetic case-control studies.
Combining identity by descent and association in genetic case-control studies.
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在遗传病例对照研究中将血统身份与关联相结合
DOI：
10.1186/1471-2156-9-42
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发表时间：
2008-07-05
期刊：
影响因子：
2.9
通讯作者：
Ott J
中科院分区：
文献类型：
--
作者：
Zhang Q;Wang S;Ott J
在人类病例对照关联研究中，通常进行的卡方检验之一是基于 2 × 3 基因型表（病例和对照个体中三种基因型频率的同质性）。我们根据两个生物学相关参数制定与给定基因型分布相关的两个自由度：(1) 个体的两个等位基因在血统上相同的概率 F (IBD) 和 (2) 其中一个等位基因的频率 p。施加限制，F ≥ 0，使一些基因型频率无效，从而减少噪音。我们提出了一种新的统计关联测试，即 FP 测试，重点关注病例和对照个体之间的等位基因频率差异，同时考虑到适当的 IBD 概率。功效计算表明（1）通常进行两种关联测试（等位基因和基因型测试）的做法会增加I型错误，并且（2）我们的测试比隐性遗传下的传统基因型和等位基因测试更强大，并且至少与显性遗传下的这些传统测试一样强大。对于显性和隐性遗传模式，当等位基因测试与基因型测试结合进行时，任何明显的功率增益往往完全是由于省略多重测试校正而导致假阳性结果率增加而导致的。作为这两个标准关联测试的替代方案，我们的 FP 测试代表了一种方便且更强大的替代方案。
In human case-control association studies, one of the chi-square tests typically carried out is based on a 2 × 3 table of genotypes (homogeneity of three genotype frequencies in case and control individuals). We formulate the two degrees of freedom associated with a given genotype distribution in terms of two biologically relevant parameters, (1) the probability F that an individual's two alleles are identical by descent (IBD) and (2) the frequency p of one of the alleles. Imposing the restriction, F ≥ 0, makes some of the genotype frequencies invalid thereby reducing noise. We propose a new statistical association test, the FP test, by focusing on allele frequency differences between case and control individuals while allowing for suitable IBD probabilities. Power calculations show that (1) the practice of generally carrying out two association tests (allele and genotype test) has an increased type I error and (2) our test is more powerful than conventional genotype and allele tests under recessive trait inheritance, and at least as powerful as these conventional tests under dominant inheritance. For dominant and recessive modes of inheritance, any apparent power gain by an allele test when carried out in conjunction with a genotype test tends to be purchased entirely by an increased rate of false positive results due to omission of a multiple testing correction. As an alternative to these two standard association tests, our FP test represents a convenient and more powerful alternative.
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影响因子：
3.5
作者：
Gibson, J;Morton, NE;Collins, A
通讯作者：
Collins, A
影响因子：
30.8
作者：
HOUWEN, RHJ;BAHARLOO, S;FREIMER, NB
通讯作者：
FREIMER, NB
影响因子：
9.8
作者：
Broman, KW;Weber, JL
通讯作者：
Weber, JL
影响因子：
56.9
作者：
DeWan, Andrew;Liu, Mugen;Hoh, Josephine
通讯作者：
Hoh, Josephine
DOI：
10.1073/pnas.170179197
发表时间：
2000-08-15
影响因子：
11.1
作者：
Hoh, J;Ott, J
通讯作者：
Ott, J