Effect of misspecification of gene frequency on the two-point LOD score

TY - JOUR

T1 - Effect of misspecification of gene frequency on the two-point LOD score

AU - Pal, D K

AU - Durner, M

AU - Greenberg, D A

PY - 2001/11

Y1 - 2001/11

N2 - In this study, we used computer simulation of simple and complex models to ask: (1) What is the penalty in evidence for linkage when the assumed gene frequency is far from the true gene frequency? (2) If the assumed model for gene frequency and inheritance are misspecified in the analysis, can this lead to a higher maximum LOD score than that obtained under the true parameters? Linkage data simulated under simple dominant, recessive, dominant and recessive with reduced penetrance, and additive models, were analysed assuming a single locus with both the correct and incorrect dominance model and assuming a range of different gene frequencies. We found that misspecifying the analysis gene frequency led to little penalty in maximum LOD score in all models examined, especially if the assumed gene frequency was lower than the generating one. Analysing linkage data assuming a gene frequency of the order of 0.01 for a dominant gene, and 0.1 for a recessive gene, appears to be a reasonable tactic in the majority of realistic situations because underestimating the gene frequency, even when the true gene frequency is high, leads to little penalty in the LOD score.

AB - In this study, we used computer simulation of simple and complex models to ask: (1) What is the penalty in evidence for linkage when the assumed gene frequency is far from the true gene frequency? (2) If the assumed model for gene frequency and inheritance are misspecified in the analysis, can this lead to a higher maximum LOD score than that obtained under the true parameters? Linkage data simulated under simple dominant, recessive, dominant and recessive with reduced penetrance, and additive models, were analysed assuming a single locus with both the correct and incorrect dominance model and assuming a range of different gene frequencies. We found that misspecifying the analysis gene frequency led to little penalty in maximum LOD score in all models examined, especially if the assumed gene frequency was lower than the generating one. Analysing linkage data assuming a gene frequency of the order of 0.01 for a dominant gene, and 0.1 for a recessive gene, appears to be a reasonable tactic in the majority of realistic situations because underestimating the gene frequency, even when the true gene frequency is high, leads to little penalty in the LOD score.

KW - Computer Simulation

KW - Female

KW - Gene Frequency

KW - Humans

KW - Lod Score

KW - Male

KW - Models, Genetic

KW - Nuclear Family

U2 - 10.1038/sj.ejhg.5200724

DO - 10.1038/sj.ejhg.5200724

M3 - Article

C2 - 11781703

SN - 1018-4813

VL - 9

SP - 855

EP - 859

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

IS - 11

ER -