Abstract

OBJECTIVE:

One of the first tools for performing linkage analysis, Haseman-Elston regression (HE), has been successfully used to identify linkages to several disease traits. A recent explosion in extensions of HE leaves one faced with the task of choosing a flavor of HE best suited for a given situation. This paper puts this dilemma into perspective and proposes a modification to HE for highly ascertained samples (BLUP-PM).

METHODS:

Using data simulated for a range of models, we evaluated type I error and power of several dependent variables in HE, including the novel BLUP-PM.

RESULTS:

When analyzing a continuous trait, even in highly ascertained samples, type I error is stable and approximately nominal across dependent variables. When analyzing binary traits in highly ascertained samples, type I error is elevated and unstable for all except BLUP-PM. Regardless of trait type, the optimally weighted HE regression and BLUP-PM have the greatest power.

CONCLUSIONS:

Ascertained samples do not always reflect the population from which they are drawn and therefore choice of dependent variable in HE becomes increasingly important. Our results do not reveal a single, universal choice, but offer criteria by which to choose and demonstrate BLUP-PM performs well in most situations.

(c) 2007 S. Karger AG, Basel.