Testing Hardy–Weinberg Equilibrium and Homogeneity of Hardy–Weinberg Disequilibrium using Complex Survey Data

Abstract

For studies on population genetics, the use of representative random samples of the target population can avoid ascertainment bias. Genetic variation data from over a hundred genes were collected in a U.S. nationally representative sample in the Third National Health and Nutrition Examination Survey (NHANES III). Surveys such as the NHANES have complex stratified multistage cluster sample designs with sample weighting that can inflate variances and alter the expectations of test statistics. Thus, classical statistical tests of Hardy-Weinberg equilibrium (HWE) and homogeneity of HW disequilibrium (HHWD) for simple random samples are not suitable for data from complex samples. We propose using Wald tests for HWE and generalized score tests for HHWD that have been modified for complex samples. Monte Carlo simulation studies are used to investigate the finite sample properties of the proposed tests. Rao-Scott corrections applied to the tests were found to improve their type I error properties. Our methods are applied to the NHANES III genetic data for three loci involved in metabolizing lead in the body.