No bias in linkage analysis.

Abecasis G, Cox N, Daly MJ, Kruglyak L, Laird N, Markianos K and Patterson N

Am J Hum Genet (2004) 75:722-3

To the Editor: We would like to comment on the Schork and Greenwood (2004) article dealing with the inherent “bias” toward the null hypothesis in the context of nonparametric linkage analysis. The authors point out that, in certain situations, a loss of evidence for linkage can result from the practice of assigning expected allele-sharing values to affected relative pairs that are uninformative for their identity-by-descent (IBD) status. They explained this by setting up a likelihood function and studying its properties by simulation, clearly illustrating the negative impact of using expected IBD values for uninformative pairs. However, we would like to point out that their likelihood does not reflect how the majority of nonparametric linkage analysis programs compute statistics in practice. Indeed, the “problem” has been known and well discussed for years. Some of the concerns we discuss here have also been raised by Cordell (2004).