Visscher P M, Thompson R, Haley C S
Roslin Institute Edinburgh, Midlothian, Scotland.
Genetics. 1996 Jun;143(2):1013-20. doi: 10.1093/genetics/143.2.1013.
The determination of empirical confidence intervals for the location of quantitative trait loci (QTLs) was investigated using simulation. Empirical confidence intervals were calculated using a bootstrap resampling method for a backcross population derived from inbred lines. Sample sizes were either 200 or 500 individuals, and the QTL explained 1, 5, or 10% of the phenotypic variance. The method worked well in that the proportion of empirical confidence intervals that contained the simulated QTL was close to expectation. In general, the confidence intervals were slightly conservatively biased. Correlations between the test statistic and the width of the confidence interval were strongly negative, so that the stronger the evidence for a QTL segregating, the smaller the empirical confidence interval for its location. The size of the average confidence interval depended heavily on the population size and the effect of the QTL. Marker spacing had only a small effect on the average empirical confidence interval. The LOD drop-off method to calculate empirical support intervals gave confidence intervals that generally were too small, in particular if confidence intervals were calculated only for samples above a certain significance threshold. The bootstrap method is easy to implement and is useful in the analysis of experimental data.
利用模拟研究了数量性状基因座（QTL）位置的经验置信区间的确定方法。对于由近交系衍生的回交群体，采用自助重抽样方法计算经验置信区间。样本量为200或500个个体，QTL解释了1%、5%或10%的表型变异。该方法效果良好，包含模拟QTL的经验置信区间的比例接近预期。一般来说，置信区间存在轻微的保守偏差。检验统计量与置信区间宽度之间的相关性为强负相关，因此QTL分离的证据越强，其位置的经验置信区间越小。平均置信区间的大小在很大程度上取决于群体大小和QTL的效应。标记间距对平均经验置信区间的影响很小。用于计算经验支持区间的LOD下降法给出的置信区间通常过小，特别是当仅对高于某个显著性阈值的样本计算置信区间时。自助法易于实施，在实验数据分析中很有用。
