Resampling-based multiple hypothesis testing procedures for genetic case-control association studies
Resampling-based multiple hypothesis testing procedures for genetic case-control association studies
复制标题
DOI：
10.1002/gepi.20162
复制
发表时间：
2006-09-01
影响因子：
2.1
通讯作者：
Rosenberg, Philip S.
中科院分区：
文献类型：
--
作者：
Chen, Bingshu E.;Sakoda, Lori C.;Rosenberg, Philip S.
在不相关受试者的病例对照研究中，基于基因的假设检验考虑候选基因中的任何被测试特征（单核苷酸多态性、单倍型或两者）是否与疾病相关。标准的统计检验可以将假阳性率控制在所考虑的所有多态性的名义水平。但是，可以构建更强大的测试，使用排列重新采样来解释多态性和测试统计信息之间的相关性。一个关键问题是，功率增益是否大到足以抵消计算负担。我们将计算简单的Simes全局检验与最小P检验进行了比较，最小P检验考虑了每个SNP的边际检验的最小P值的排列分布。在包含15个基因的经验单倍型结构的模拟研究中，最小P检验控制了I型误差，并且比Simes检验平均强2.1个百分点。当单倍型赋予疾病易感性时，最小P检验有时（但并非总是）表现不佳。基于重采样的综合检验结合最小P和单倍型频率检验控制了I型误差，并密切跟踪了两种成分检验中较强的成分。与Simes和单倍型分析的简单Bonferroni测试相比，该测试获得了一致的功率增益（平均5.7个百分点）。根据上海胆道肿瘤研究的数据，在一项基于人群的胆管癌和前列腺素内过氧化物合成酶2 （PTGS2）基因多态性研究中，新提出的综合检测的优势是显而易见的。麝猫。中华流行病学杂志，2006。2006年Wiley-Liss出版。
In case-control studies of unrelated subjects, gene-based hypothesis tests consider whether any tested feature in a candidate gene single nucleotide polymorphisms (SNPs), haplotypes, or both-are associated with disease. Standard statistical tests are available that control the false-positive rate at the nominal level over all polymorphisms considered. However, more powerful tests can be constructed that use permutation resampling to account for correlations between polymorphisms and test statistics. A key question is whether the gain in power is large enough to justify the computational burden. We compared the computationally simple Simes Global Test to the min P test, which considers the permutation distribution of the minimum p-value from marginal tests of each SNP. In simulation studies incorporating empirical haplotype structures in 15 genes, the min P test controlled the type I error, and was modestly more powerful than the Simes test, by 2.1 percentage points on average. When disease susceptibility was conferred by a haplotype, the min P test sometimes, but not always, under-performed haplotype analysis. A resampling-based omnibus test combining the min P and haplotype frequency test controlled the type I error, and closely tracked the more powerful of the two component tests. This test achieved consistent gains in power (5.7 percentage points on average), compared to a simple Bonferroni test of Simes and haplotype analysis. Using data from the Shanghai Biliary Tract Cancer Study, the advantages of the newly proposed omnibus test were apparent in a population-based study of bile duct cancer and polymorphisms in the prostaglandin-endoperoxide synthase 2 (PTGS2) gene. Genet. Epidemiol. 30:495-507, 2006. Published 2006 Wiley-Liss, Inc.