THE EFFECT OF MISSPECIFYING ALLELE FREQUENCIES IN INCOMPLETELY TYPED FAMILIES

To examine the effect of a misspecified marker allele frequency, the s egregation of a marker unlinked to Alzheimer's disease was simulated f or the typed members of the GAW8-FAD4 pedigree. Lod scores were calcul ated for different assumed marker allele frequencies. The results show that a misspecification of marker frequency can lead to spuriously hi gh lod scores. The affecteds-only method for linkage analysis is even more sensitive in regard to marker frequency misspecification. Therefo re, we recommend estimation of marker allele frequencies from the actu al family data. The simple estimator we considered in this paper seems to be sufficient. (C) 1993 Wiley-Liss, Inc.