A comparison of tests for Hardy-Weinberg Equilibrium in national genetic household surveys

Background: This study is motivated by National Household Surveys that collect genetic data, in which complex samples (e. g. stratified multistage cluster sample), partially from the same family, are selected. In addition to the differential selection probabilities of selecting households and persons within the sampled households, there are two levels of correlations of the collected genetic data in National Genetic Household Surveys (NGHS). The first level of correlation is induced by the hierarchical geographic clustered sampling of households and the second level of correlation is induced by biological inheritances from individuals sampled in the same household. Results: To test for Hardy-Weinberg Equilibrium (HWE) in NGHS, two test statistics, the CCS method [1] and the QS method [2], appear to be the only existing methods that take account of both correlations. In this paper, I evaluate both methods in terms of the test size and power under a variety of complex designs with different weighting schemes and varying magnitudes of the two correlation effects. Both methods are applied to a real data example from the Hispanic Health and Nutrition Examination Survey with simulated genotype data. Conclusions: The QS method maintains the nominal size well and consistently achieves higher power than the CCS method in testing HWE under a variety of sample designs, and therefore is recommended for testing HWE of genetic survey data with complex designs.