Case-control association testing with related individuals: A more powerful quasi-likelihood score test
Case-control association testing with related individuals: A more powerful quasi-likelihood score test
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DOI：
10.1086/519497
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发表时间：
2007-08-01
影响因子：
9.8
通讯作者：
McPeek, Mary Sara
中科院分区：
文献类型：
--
作者：
Thornton, Tirnothy;McPeek, Mary Sara
我们考虑的问题，全基因组关联测试的二元性状时，一些抽样的个人有关，与已知的关系。这通常发生在为连锁研究抽样的家系被包括在关联研究中时。此外，当受影响的个体与受影响的亲属被抽样时，检测与复杂性状的关联的能力可以增加，因为他们比随机抽样的受影响个体更可能携带疾病等位基因。对于相关个体，必须考虑亲属之间的相关性，以确保测试的有效性，并且考虑这些相关性也可以提高功效。我们提供了新的见解，使用pecligree为基础的权重，以提高功率，我们提出了一种新的测试，M，测试，其中，正如我们所展示的，代表了一个整体，在许多情况下，实质性的，改善功率比以前的测试，同时保留计算简单，使其有用的全基因组关联研究在任意谱系。M-QLS的其他特征如下：（1）它适用于家庭和病例对照设计的完全一般组合，（2）它可以将未受影响的对照和未知表型的对照纳入同一分析，以及（3）它可以纳入缺失基因型数据的亲属的表型数据。这些方法应用于遗传分析研讨会14酒精中毒遗传学合作研究的数据，其中M-QLs检测全基因组显著关联（Bonferroni校正后）具有酗酒相关表型的四种不同的单核苷酸多态性：tsc 1177811（p = 5.9 × 10（-7））、tsc 1750530（P = 4.0 × 10-7）、tsc 0046696（P = 4.7 × 10-7）和tsc 0057290（P = 5.2 × 10（-1））分别位于1、16、18和18号染色体上。这四个显著关联中的三个在以前分析这些数据的研究中没有检测到。
We consider the problem of genomewide association testing of a binary trait when some sampled individuals are related, with known relationships. This commonly arises when families sampled for a linkage study are included in an association studv. Furthermore, power to detect association with complex traits can be increased when affected individuals with affected relatives are sampled, because they are more likely to carry disease alleles than are randomly sampled affected individuals. With related individuals, correlations among relatives must be taken into account, to ensure validity of the test, and consideration of these correlations can also improve power. We provide new insight into the use of pecligree-based weights to improve power, and we propose a novel test, the M,,,,, test, which, as we demonstrate, represents an overall, and in many cases, substantial, improvement in power over previous tests, while retaining a computational simplicity that makes it useful in genomewide association studies in arbitrary pedigrees. Other features of the M-QLS, are as follows: (1) it is applicable to completely general combinations of family and case-control designs, (2) it can incorporate both unaffected controls and controls of unknown phenotype into the same analysis, and (3) it can incorporate phenotype data about relatives with missing genotype data. The methods are applied to data from the Genetic Analysis Workshop 14 Collaborative Study of the Genetics of Alcoholism, where the M-QLs detects genomewide significant association (after Bonferroni correction) with an alcoholism-related phenotype for four different single-nucleotide polymorphisms: tsc1177811 (p = 5.9 X 10(-7)), tsc1750530 (P = 4.0 x 10-7), tsc0046696 (P = 4.7 x 10-7), and tsc0057290 (P = 5.2 x 10(-1)) on chromosomes 1, 16, 18, and 18, respectively. Three of these four significant associations were not detected in previous studies analyzing these data.