Percentiles of the null distribution of 2 maximum lod score tests

• Published in: Human heredity Vol. 57; no. 1; p. 39
• Main Authors: Ulgen, Ayse, Yoo, Yun Joo, Gordon, Derek, Finch, Stephen J, Mendell, Nancy R
• Format: Journal Article
• Language: English
• Published: Switzerland 01-01-2004
• Subjects: Alleles; Genetic Linkage; Genotype; Humans; Likelihood Functions; Linkage Disequilibrium; Lod Score; Models, Genetic; Models, Statistical; Recombination, Genetic; Statistics, Nonparametric; Time Factors
• ISSN: 0001-5652
• DOI: 10.1159/000077388

We here consider the null distribution of the maximum lod score (LOD-M) obtained upon maximizing over transmission model parameters (penetrance values, dominance, and allele frequency) as well as the recombination fraction. Also considered is the lod score maximized over a fixed choice of genetic model parameters and recombination-fraction values set prior to the analysis (MMLS) as proposed by Hodge et al. The objective is to fit parametric distributions to MMLS and LOD-M. Our results are based on 3,600 simulations of samples of n = 100 nuclear families ascertained for having one affected member and at least one other sibling available for linkage analysis. Each null distribution is approximately a mixture p(2)(0) + (1 - p)(2)(v). The values of MMLS appear to fit the mixture 0.20(2)(0) + 0.80chi(2)(1.6). The mixture distribution 0.13(2)(0) + 0.87chi(2)(2.8). appears to describe the null distribution of LOD-M. From these results we derive a simple method for obtaining critical values of LOD-M and MMLS.