Comparison of type I error for multiple test corrections in large single-nucleotide polymorphism studies using principal components versus haplotype blocking algorithms.
Comparison of type I error for multiple test corrections in large single-nucleotide polymorphism studies using principal components versus haplotype blocking algorithms.
复制标题
使用主成分与单倍型阻断算法对大型单核苷酸多态性研究中多次测试校正的 I 型错误进行比较。
DOI：
10.1186/1471-2156-6-s1-s78
复制
发表时间：
2005-12-30
期刊：
影响因子：
2.9
通讯作者：
Fallin, MD
中科院分区：
文献类型：
--
作者：
Nicodemus, KK;Liu, WL;Chase, GA;Tsai, YY;Fallin, MD
尽管置换测试已经成为评估使用多个标记的研究中显着性水平的金标准，但它很耗时。最近提出了对标称p值的Bonferroni校正，该校正使用标记之间的基本成对连锁不平衡(LD)结构来确定有效独立测试的数量。我们建议使用独立LD区块的数量加上独立单核苷酸多态的数量来进行校正。使用21号染色体酒精中毒LD数据的遗传学合作研究，我们模拟了在零假设和两个LD水平：中等和高LD下的1000个重复的亲子三重数据。假设单倍型区块是独立的，我们使用3个单倍型区块算法计算了独立统计检验的数量。然后，我们使用基于主成分的方法、三种分块方法、传统的Bonferroni校正和从FBAT获得的未经调整的p值来比较I类错误率。在高LD条件下，PC方法和其中一种阻塞方法略显保守，而其他两种阻塞方法超过了目标I类错误率。在中等LD条件下，我们证明了块算法修正最接近理想的第I类误差，但仍略显保守，而基于主成分的方法几乎与传统的Bonferroni修正一样保守。
Although permutation testing has been the gold standard for assessing significance levels in studies using multiple markers, it is time-consuming. A Bonferroni correction to the nominal p-value that uses the underlying pair-wise linkage disequilibrium (LD) structure among the markers to determine the number of effectively independent tests has recently been proposed. We propose using the number of independent LD blocks plus the number of independent single-nucleotide polymorphisms for correction. Using the Collaborative Study on the Genetics of Alcoholism LD data for chromosome 21, we simulated 1,000 replicates of parent-child trio data under the null hypothesis with two levels of LD: moderate and high. Assuming haplotype blocks were independent, we calculated the number of independent statistical tests using 3 haplotype blocking algorithms. We then compared the type I error rates using a principal components-based method, the three blocking methods, a traditional Bonferroni correction, and the unadjusted p-values obtained from FBAT. Under high LD conditions, the PC method and one of the blocking methods were slightly conservative, whereas the 2 other blocking methods exceeded the target type I error rate. Under conditions of moderate LD, we show that the blocking algorithm corrections are closest to the desired type I error, although still slightly conservative, with the principal components-based method being almost as conservative as the traditional Bonferroni correction.