在存在基因型错误和缺失父母数据的情况下的精度和 I 型错误率：原始传递不平衡检验（TDT）和 TDTae 统计量的比较。

Precision and type I error rate in the presence of genotype errors and missing parental data: a comparison between the original transmission disequilibrium test (TDT) and TDTae statistics.

机构信息

Laboratory of Statistical Genetics, Rockefeller University, New York, NY 10021, USA.

出版信息

BMC Genet. 2005 Dec 30;6 Suppl 1(Suppl 1):S150. doi: 10.1186/1471-2156-6-S1-S150.

DOI:10.1186/1471-2156-6-S1-S150

PMID:16451611

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1866784/

Abstract

BACKGROUND

Two factors impacting robustness of the original transmission disequilibrium test (TDT) are: i) missing parental genotypes and ii) undetected genotype errors. While it is known that independently these factors can inflate false-positive rates for the original TDT, no study has considered either the joint impact of these factors on false-positive rates or the precision score of TDT statistics regarding these factors. By precision score, we mean the absolute difference between disease gene position and the position of markers whose TDT statistic exceeds some threshold.

METHODS

We apply our transmission disequilibrium test allowing for errors (TDTae) and the original TDT to phenotype and modified single-nucleotide polymorphism genotype simulation data from Genetic Analysis Workshop. We modify genotype data by randomly introducing genotype errors and removing a percentage of parental genotype data. We compute empirical distributions of each statistic's precision score for a chromosome harboring a simulated disease locus. We also consider inflation in type I error by studying markers on a chromosome harboring no disease locus.

RESULTS

The TDTae shows median precision scores of approximately 13 cM, 2 cM, 0 cM, and 0 cM at the 5%, 1%, 0.1%, and 0.01% significance levels, respectively. By contrast, the original TDT shows median precision scores of approximately 23 cM, 21 cM, 15 cM, and 7 cM at the corresponding significance levels, respectively. For null chromosomes, the original TDT falsely rejects the null hypothesis for 28.8%, 14.8%, 5.4%, and 1.7% at the 5%, 1%, 0.1% and 0.01%, significance levels, respectively, while TDTae maintains the correct false-positive rate.

CONCLUSION

Because missing parental genotypes and undetected genotype errors are unknown to the investigator, but are expected to be increasingly prevalent in multilocus datasets, we strongly recommend TDTae methods as a standard procedure, particularly where stricter significance levels are required.

摘要

背景

影响原始传递不平衡检验（TDT）稳健性的两个因素是：i）缺失的父母基因型和 ii）未检测到的基因型错误。虽然已知这两个因素独立地会增加原始 TDT 的假阳性率，但没有研究考虑这两个因素对假阳性率的联合影响，也没有研究 TDT 统计量在这些因素下的精度得分。精度得分是指疾病基因位置与 TDT 统计量超过某个阈值的标记位置之间的绝对差异。

方法

我们应用我们的允许存在误差的传递不平衡检验（TDTae）和原始 TDT，对来自遗传分析研讨会的表型和修改后的单核苷酸多态性基因型模拟数据进行分析。我们通过随机引入基因型错误和删除一定比例的父母基因型数据来修改基因型数据。我们计算了每个统计量在包含模拟疾病基因座的染色体上的精度得分的经验分布。我们还通过研究不包含疾病基因座的染色体上的标记来研究第一类错误的膨胀。

结果

TDTae 在 5%、1%、0.1%和 0.01%的显著水平下，分别具有约 13、2、0 和 0 cM 的中位数精度得分；相比之下，原始 TDT 在相应的显著水平下分别具有约 23、21、15 和 7 cM 的中位数精度得分。对于零染色体，原始 TDT 在 5%、1%、0.1%和 0.01%的显著水平下，错误地拒绝零假设的比例分别为 28.8%、14.8%、5.4%和 1.7%，而 TDTae 保持了正确的假阳性率。