Ascertainment-adjusted parameter estimates revisited.

Ascertainment-adjusted parameter estimates from a genetic analysis are typically assumed to reflect the parameter values in the original population from which the ascertained data were collected. Burton et al. (2000) recently showed that, given unmodeled parameter heterogeneity, the standard ascertainment adjustment leads to biased parameter estimates of the population-based values. This finding has important implications in complex genetic studies, because of the potential existence of unmodeled genetic parameter heterogeneity. The authors further stated the important point that, given unmodeled heterogeneity, the ascertainment-adjusted parameter estimates reflect the true parameter values in the ascertained subpopulation. They illustrated these statements with two examples. By revisiting these examples, we demonstrate that if the ascertainment scheme and the nature of the data can be correctly modeled, then an ascertainment-adjusted analysis returns population-based parameter estimates. We further demonstrate that if the ascertainment scheme and data cannot be modeled properly, then the resulting ascertainment-adjusted analysis produces parameter estimates that generally do not reflect the true values in either the original population or the ascertained subpopulation.