Weeks D E, Lehner T, Squires-Wheeler E, Kaufmann C, Ott J
New York State Psychiatric Institute Department of Psychiatry, Columbia University, New York, NY 10032.
Genet Epidemiol. 1990;7(4):237-43. doi: 10.1002/gepi.1370070402.
A computer-simulation method is presented for determining and correcting for the effect of maximizing the lod score over disease definitions, penetrance values, and perhaps other model parameters. The method consists of simulating the complete analysis using marker genotypes randomly generated under the assumption of free recombination. It is applicable as a "post-treatment" to linkage analyses of any trait with an uncertain mode of inheritance and/or disease definition. When the method is applied to a linkage analysis of schizophrenia versus chromosome 5 markers, we find that, in this specific case, the P-value associated with a maximum lod score of 3 is equal to 0.0003. We also find that a lod score of 3.0 should be "deflated" by approximately 0.3 to 1 units, and, by tentative extrapolation, the observed lod score of 6.5 should be "deflated" by 0.7 to 1.5 units.
本文提出了一种计算机模拟方法，用于确定和校正因疾病定义、外显率值以及其他可能的模型参数而使对数优势比分最大化所产生的影响。该方法包括在自由重组假设下随机生成标记基因型，从而模拟完整的分析过程。它适用于对任何遗传模式不确定和/或疾病定义不明确的性状进行连锁分析的“后处理”。当将该方法应用于精神分裂症与5号染色体标记的连锁分析时，我们发现在这个特定案例中，与最大对数优势比分3相关的P值等于0.0003。我们还发现，对数优势比分3.0应“下调”约0.3至1个单位，通过初步推断，观察到的对数优势比分6.5应“下调”0.7至1.5个单位。
