Don't over estimate the power....

A lucid example of why one should not treat estimated haplotypes as observed haplotypes has been provided by David Curtis and Pak Sham in a letter to the American Journal of Human Genetics.

They demonstrate through a simple example, and simulations that the method of Zhao et al's (2005) entropy based approach, and that of Sham and Curtis (1995) both of which essentially treat estimated haplotypes as observed, are anticonservative (i.e. over estimate any association/effect).

However in the same issue Zhao et al (2006) provide a counter example , and claim that the range of haplotype frequencies that have been investigated to date is too small, and suggest that further theoretical work is required on this area.

References

Curtis D, Sham P (2006) Estimated Haplotype Counts from Case-Control Samples Cannot Be Treated as Observed Counts. American Journal of Human Genetics 78:729-730

Zhao J, Boerwinkle E, Xiong M (2006) Impact of Haplotype-Frequency Estimation Error on Test Statistics in Association Studies. American Journal of Human Genetics 78:728-729

Zhao J, Boerwinkle E, Xiong M (2005) An entropy-based statistic for genomewide association studies American Journal of Human Genetics 77:27-40