Comparison of a multipoint identity-by-descent method with parametric multipoint linkage analysis for mapping quantitative traits.
We previously developed a method of partitioning genetic variance of a quantitative trait to loci in specific chromosomal regions. In this paper, we compare this method--multipoint IBD (identical by descent) method (MIM)--with parametric multipoint linkage analysis (MLINK). A simulation study was performed comparing the methods for the major-locus, mixed, and two-locus models. The criterion for comparisons between MIM and MLINK was the average lod score from multiple replicates of simulated data sets. The effect of gene frequency, dominance, model misspecification, marker spacing, and informativeness are also considered in a smaller set of simulations. Within the context of the models examined, the MIM approach was found to be comparable in power with parametric multipoint linkage analysis when (a) parental data are unknown, (b) the effect of the major locus is small and there is additional genetic variation, or (c) the parameters of the major-locus model are misspecified. The performance of the MIM method relative to MLINK was markedly lower when the allele frequency at the trait locus was .2 versus .5, particularly for the case when parental data were assumed to be known. Dominance at the trait major locus, as well as marker spacing and heterozygosity, did not appear to have a large effect on the ELOD comparisons.
Goldgar
D E
DE
Department of Medical Informatics, University of Utah, Salt Lake City.
Oniki
R S
RS
D002874:Chromosome Mapping / Q000379:methods*; D003198:Computer Simulation; D015986:Confounding Factors, Epidemiologic; D005787:Gene Frequency; D005799:Genes, Dominant; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers; D014644:Genetic Variation; D006801:Humans; D016013:Likelihood Functions; D008126:Lod Score; D008957:Models, Genetic; D010290:Parents
D005819:Genetic Markers