A Hardy-Weinberg Equilibrium Test for Analyzing Population Genetic Surveys With Complex Sample Designs

Testing for deviations from Hardy-Weinberg equilibrium is a widely recommended practice for population-based genetic association studies. However, current methods for this test assume a simple random sample and may not be appropriate for sample surveys with complex survey designs. In this paper, the authors present a test for Hardy-Weinberg equilibrium that adjusts for the sample weights and correlation of data collected in complex surveys. The authors perform this test by using a simple adjustment to procedures developed to analyze data from complex survey designs available within the SAS statistical software package (SAS Institute, Inc., Cary, North Carolina). Using 90 genetic markers from the Third National Health and Nutrition Examination Survey, the authors found that survey-adjusted and -unadjusted estimates of the disequilibrium coefficient were generally similar within self-reported races/ethnicities. However, estimates of the variance of the disequilibrium coefficient were significantly different between the 2 methods. Because the results of the survey-adjusted tests account for correlation among participants sampled within the same cluster, and the possibility of having related individuals sampled from the same household, the authors recommend use of this test when analyzing genetic data originating from sample surveys with complex survey designs to assess deviations from Hardy-Weinberg equilibrium.