The impact of marker allele frequency misspecification in variance components quantitative trait locus analysis using sibship data

In cases where sibship data are collected for a quantitative trait locus (Q TL) linkage study without access to parental genotypes, the proportion of g enes shared identical by descent must be estimated using the marker allele frequencies. No systematic study has been conducted to date to evaluate the effect of misspecification of these frequencies on a test of quantitative trait linkage. Analysis of both simulated and actual data on quantitative t raits was carried out under various sets of allele frequency estimates. Whi le correctly specifying the allele frequency distribution led to a slightly more powerful test and higher lod scores, the differences were small and w ould not likely alter the conclusion of a study. These results suggest that , at least for QTL analysis, there is a great deal of tolerance for misspec ifying marker allele frequencies with little, if any, appreciable effect on the linkage test. However, the observed variations may be sufficiently lar ge to alter the priority one might give to a positive finding for follow up . (C) 1999 Wiley-Liss, Inc.