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 pχ02 + (1 - p) χv2. The values of MMLS appear to fit the mixture 0.20χ02 + 0.80χ1.62. The mixture distribution 0.13χ02 + 0.87χ 2.82. 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.
All Science Journal Classification (ASJC) codes
- Asymptotic distribution
- Statistical genetics