Kong A, Frigge M, Irwin M, Cox N
Department of Statistics, University of Chicago, IL 60637.
Am J Hum Genet. 1992 Dec;51(6):1413-29.
In linkage analysis, when the lod score is maximized over multiple genetic models, standard asymptotic approximation of the significance level does not apply. Monte Carlo methods can be used to estimate the p value, but procedures currently used are extremely inefficient. We propose a Monte Carlo procedure based on the concept of importance sampling, which can be thousands of times more efficient than current procedures. With a reasonable amount of computing time, extremely accurate estimates of the p values can be obtained. Both theoretical results and an example of maturity-onset diabetes of the young (MODY) are presented to illustrate the efficiency performance of our method. Relations between single-model and multimodel p values are explored. The new procedure is also used to investigate the performance of asymptotic approximations in a single model situation.
在连锁分析中，当对数优势比分（lod score）在多个遗传模型上达到最大值时，显著性水平的标准渐近近似法并不适用。蒙特卡罗方法可用于估计p值，但目前使用的程序效率极低。我们提出了一种基于重要性抽样概念的蒙特卡罗程序，其效率可比当前程序高出数千倍。只需合理的计算时间，就能获得极其精确的p值估计。本文给出了理论结果以及一个青少年发病的成年型糖尿病（MODY）的例子，以说明我们方法的效率表现。还探讨了单模型和多模型p值之间的关系。新程序也用于研究单模型情况下渐近近似法的性能。
