Visscher Peter M, Goddard Mike E
Institute of Cell, Animal and Population Biology, University of Edinburgh, Edinburgh, UK.
Behav Genet. 2004 Jul;34(4):477-82. doi: 10.1023/B:BEGE.0000023652.93162.e8.
In 1997, Darvasi and Soller presented empirical predictions of the confidence interval of quantitative trait loci (QTL) location for dense marker maps in experimental crosses. They showed from simulation results for backcross and F2 populations from inbred lines that the 95% confidence interval was a simple function of sample size and the effect of the QTL. In this study, we derive by theory simple equations that can be used to predict any confidence interval and show that for the 95% confidence interval, they are in good agreement with the empirical results given by Darvasi and Soller. A general form of the confidence interval is given that also applies to other population structures (e.g., collections of sib pairs). Furthermore, the expected shape of the likelihood-ratio-test around the true QTL location is derived, which is shown to be extremely leptokurtic. It is shown that this shape explains why confidence intervals from the Log of Odds (LOD) drop-off method and bootstrap results frequently differ for real data sets.
1997年,达尔瓦西和索勒给出了实验杂交中密集标记图谱数量性状基因座(QTL)定位置信区间的实证预测。他们从近交系回交和F2群体的模拟结果表明,95%置信区间是样本量和QTL效应的简单函数。在本研究中,我们通过理论推导得出可用于预测任何置信区间的简单方程,并表明对于95%置信区间,这些方程与达尔瓦西和索勒给出的实证结果高度一致。给出了置信区间的一般形式,该形式也适用于其他群体结构(如同胞对集合)。此外,推导了真实QTL位置周围似然比检验的预期形状,结果表明其具有极高的峰度。结果表明,这种形状解释了为什么对于实际数据集,来自优势对数(LOD)下降法的置信区间和自举结果常常不同。