During this fiscal year, this project, originally begun when Dr. Bailey-Wilson was a Professor at Louisiana State University Medical Center, has been continued. The project is designed to use computer simulation techniques to determine the power and robustness of several types of linkage analysis to various failures of assumptions.
The aims of the study are to 1) evaluate the Type I error rates of non-parametric Haseman-Elston sib-pair linkage analysis of both quantitative and qualitative traits (with and without environmental covariates) to misspecification of marker locus allele frequencies when parental data are missing; 2) to determine and compare the power of both Haseman-Elston sib-pair linkage and parametric lod-score linkage for both quantitative and qualitative traits under a variety of misspecifications of the trait and marker loci; 3) to eventually include other methods of linkage analysis in these comparisons. To date, Type I error rates for a quantitative trait with high heritability and no environmental covariates has been determined for the H-E test when marker alleles are misspecified. In general the H-E test is very robust to this sort of misspecification when using modern marker loci (at least 5 this same quantitative trait has been determined for both the H-E and the lod-score tests when marker allele frequencies are misspecified. When modern markers are used, the effect of misspecification on power is small for both methods, with the effect often beimg less pronounced for the H alleles with high heterozygosity). Power for-E test. We have also shown that powerof the lod-score method is drastically reduced by only small to moderate misspecifications trait locus genotypic means. We have also shown that very small misspecifications in the trait model combined with small to moderate misspecifications in marker allele frequencies are sufficient to cause large increass in Type I error submission for publication and a third is in develoment at present.
| Mandal, D M; Wilson, A F; Elston, R C et al. (2000) Effects of misspecification of allele frequencies on the type I error rate of model-free linkage analysis. Hum Hered 50:126-32 |
| Mandal, D M; Sorant, A J; Pugh, E W et al. (1999) Environmental covariates: effects on the power of sib-pair linkage methods. Genet Epidemiol 17 Suppl 1:S643-8 |
