Ascertainment issues in variance components models

One of the main concerns in the family studies of complex diseases is the e ffect that ascertainment and correction for it may have on test procedures and estimators. Elston and Sobel [1979] and Hopper and Mathews [1982] propo sed two ways to correct for ascertainment in the study of quantitative trai t data. For single ascertainment, using a variance components approach, we present results of simulation studies comparing estimates from these two me thods for different selection criteria. We also show results from simulatio ns when ascertained families are analyzed either at random or by correcting for ascertainment. For discordant sibpairs, we compare a variance componen ts model that incorporates ascertainment correction with the extreme discor dant sib pairs (EDSP) design proposed by Risch and Zhang [1995]. Our result s show that there is minimal difference between the two methods of ascertai nment correction. In the presence of effects from a large genetic backgroun d and the segregation of a rare gene, both ascertainment affected the polyg enic 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 proce dures for common alleles, and the variance components procedure is much mor e powerful than using EDSP when there is a rare allele segregating in the p opulation. (C) 2000 Wiley-Liss, Inc.