The effect of misspecifying allele frequencies in incompletely typed families.

To examine the effect of a misspecified marker allele frequency, the segregation of a marker unlinked to Alzheimer's disease was simulated for the typed members of the GAW8-FAD4 pedigree. Lod scores were calculated for different assumed marker allele frequencies. The results show that a misspecification of marker frequency can lead to spuriously high lod scores. The affecteds-only method for linkage analysis is even more sensitive in regard to marker frequency misspecification. Therefore, we recommend estimation of marker allele frequencies from the actual family data. The simple estimator we considered in this paper seems to be sufficient.