Impact of genotyping errors on the type I error rate and the power of haplotype-based association methods.
Impact of genotyping errors on the type I error rate and the power of haplotype-based association methods.
复制标题
DOI：
10.1186/1471-2156-10-3
复制
发表时间：
2009-01-29
期刊：
影响因子：
2.9
通讯作者：
Chang-Claude J
中科院分区：
文献类型：
--
作者：
Marquard V;Beckmann L;Heid IM;Lamina C;Chang-Claude J
我们研究了基因分型误差对用于候选区域的两种基于单倍型的关联方法的I型错误率和经验功率的影响。我们比较了Mantel Statistic Using Haplotype Sharing和Haplotype based score test与Armitage trend test的性能。我们的研究基于1000个模拟病例对照数据设置的复制，分别有500个病例和500个对照。其中一个被检测的标记被设置为疾病位点，模拟优势比为3。差异和非差异基因分型错误是根据一个错误分类模型引入的，每个基因座的平均错误率在0.2%至15.6%之间。我们发现，在存在非差异基因分型错误和低错误率的情况下，所有三个检验统计量的I型错误率均保持名义显著性水平。对于高错误率和差异错误率，所有三个测试统计的I型错误率都被夸大了，甚至当不符合Hardy-Weinberg平衡的遗传标记被删除时也是如此。当基因分型错误率较低时，所有三种关联检验统计量的经验功率仍然很高，约为89%至94%，但在高基因分型错误率和非差异基因分型错误率时，其经验功率降至48%至80%。目前候选基因分析的实际基因分型错误率（每个基因座的平均错误率为0.2%）对I型错误率以及所有三种所调查的检验统计量的有效性没有显著问题。
We investigated the influence of genotyping errors on the type I error rate and empirical power of two haplotype based association methods applied to candidate regions. We compared the performance of the Mantel Statistic Using Haplotype Sharing and the haplotype frequency based score test with that of the Armitage trend test. Our study is based on 1000 replication of simulated case-control data settings with 500 cases and 500 controls, respectively. One of the examined markers was set to be the disease locus with a simulated odds ratio of 3. Differential and non-differential genotyping errors were introduced following a misclassification model with varying mean error rates per locus in the range of 0.2% to 15.6%. We found that the type I error rate of all three test statistics hold the nominal significance level in the presence of nondifferential genotyping errors and low error rates. For high and differential error rates, the type I error rate of all three test statistics was inflated, even when genetic markers not in Hardy-Weinberg Equilibrium were removed. The empirical power of all three association test statistics remained high at around 89% to 94% when genotyping error rates were low, but decreased to 48% to 80% for high and nondifferential genotyping error rates. Currently realistic genotyping error rates for candidate gene analysis (mean error rate per locus of 0.2%) pose no significant problem for the type I error rate as well as the power of all three investigated test statistics.
登录
查看更多内容
影响因子：
1.8
作者：
Liu, WL;Zhao, W;Chase, GA
通讯作者：
Chase, GA
影响因子：
2.9
作者：
Quade SR;Elston RC;Goddard KA
通讯作者：
Goddard KA
影响因子：
2.1
作者：
Govindarajulu, Usha S.;Spiegelman, Donna;Kraft, Peter
通讯作者：
Kraft, Peter
影响因子：
1.8
作者：
Cox, DG;Kraft, P
通讯作者：
Kraft, P
影响因子：
2.1
作者：
Sha, QY;Dong, JP;Zhang, SL
通讯作者：
Zhang, SL