### To test or not to test that is the question

A recent paper by Zou & Donner (2006) questions whether testing for Hardy-Weinberg equilibrium (HW-eqm)case-control association studies is a viable strategy.

The main point they make is that genotyping error is unlikely to be detected by testing for departure from HW-eqm. This is for a number of reasons, the assumptions underlying HW-eqm, and secondly (perhaps more importantly) that by performing a two stage analysis of screening for deviations for HW-eqm and then only taking forward markers which do not deviate inflates the Type 1 Error rate, because the p-value can not be interpreted as evidence that alleles are independent (i.e. HW-eqm holds).

This is of course appealing as it reduces the computational burden (particuarly when performing whole genome screens by association where multiple testing becomes a big problem), but also because a large proportion of associations are seen where loci do deviate from HW-eqm.

The authors propose a new test for adjusted χ^{2} test based on the difference in variance of the estimated allele frequencies in cases and controls which essentially is essentially the same as a Cochran-Armitage trend test (Sassieni, 1977). The power and performance of this test is discussed in a upcoming paper in *Annals of Human Genetics* (Ahn *et al* 2007).

So the upshot of all of this is that as a first pass screen your probably better of using a robust test rather than worrying about deviations from Hardy-Weinberg equilibrium.

## References and Links

Zou GY, Donnet A (2006) The Merits of Testing Hardy-Weinberg Equilibrium in the Analysis of Unmatched Case-Control Data: A Cautionary Note

*Annals of Human Genetics***70**:923-933

Ahn K, Haynes C, Kim W, Fleur RS, Gordon D, Finch SJ (2007) The Effects of SNP Genotyping Errors on the Power of the Cochran-Armitage Linear Trend Test for Case/Control Association Studies.

*Annals of Human Genetics***AOP**:

Sassieni PD (1997) From genotype to genes: doubling the sample size

**53**:1253-1261