Ascertainment issues in variance components models

One of the main concerns in the family studies of complex diseases is the effect that ascertainment and correction for it may have on test procedures and estimators. Elston and Sobel [1979] and Hopper and Mathews [1982] proposed two ways to correct for ascertainment in the study of quantitative trait data. For single ascertainment, using a variance components approach, we present results of simulation studies comparing estimates from these two methods for different selection criteria. We also show results from simulations when ascertained families are analyzed either at random or by correcting for ascertainment. For discordant sibpairs, we compare a variance components model that incorporates ascertainment correction with the extreme discordant sib pairs (EDSP) design proposed by Risch and Zhang [1995]. Our results show that there is minimal difference between the two methods of ascertainment correction. In the presence of effects from a large genetic background and the segregation of a rare gene, both ascertainment affected the polygenic and environmental components of variance but had rather little impact on the estimate of the linked major gene component of variance. The results also show the EDSP is slightly more powerful the variance components procedures for common alleles, and the variance components procedure is much more powerful than using EDSP when there is a rare allele segregating in the population. Genet. Epidemiol. 19:333–344, 2000. © 2000 Wiley‐Liss, Inc.