利用不一致同胞数据作定量性状的关联检验(英文)

Testing Association for a Quantitative Trait Locus Using Discordant Sibship Data

为检验定量位点和单个标记位点的等位基因之间的关联性, Schork等[2000]提出了一个odds ratio检验,这个检验是基于抽取不相干“病例”和“对照”个体.但是该检验会因人群混合或分层的影响而失效.受Risch.Zhang[1995]和Schork等[2000]的启发,我们考虑采用非一致同胞数据,并提出一个简单的检验方法.由于该检验是基于家庭的,对人群混合或分层不敏感.该检验很容易推广到多个标记位点的情形,并可以利用所有的含有至少一个“病例”个体和一个“对照”个体的同胞数据.通过数值计算讨论了检验的统计性质,特别研究了高分位点和低分位点(用来定义非一致同胞)的选取对检验功效的影响,讨论的结果对实际应用具有指导作用.进一步的随机模拟表明,利用多个标记位点数据能够明显地提高功效.此外,通过随机模拟比较了文中提出的检验和Allison等[1999]的检验的功效.结果显示,如果适当地选取两个分位点,我们的检验更有效.

Schork et al. [2000] proposed an odds ratio test for association between alleles at quantitative trait locus and a single marker. The odds ratio test was based on sampling unrelated ' case ' and ' control ' subjects. Bur this test suffers from population mixture or stratification. Motivated by Risch and Zhang [1995] and Schork et al. [2000], we consider the sampling from discordant sibships and propose a simple test for QTL-marker allele association. The proposed test is not sensitive to population mixture or stratification since it is family-based. The test can be easily extended to multilocus case, and to involving in any sibships with at least one case sibling and one control sibling. Some statistical properties of the tests are studied by means of numerical calculations. We especially study how the choice of uper and lower percentiles, which define the discordant sibships, affects the power of the test. The results may be helpful in practice. Additional simulations show that the multiloci test can signifieantly improve the power. To compare the power of our test and that of Allison et al. [1999]. some simulations are performed. The simulation results show that our test performs better provided the uper and lower percenriles are properly chosen.