Hardy Weinberg Equilibrium Testing and Interpretation: Focus on infection

Hardy-Weinberg equilibrium (HWE) holds when, in a closed population with random mating and without mutation and natural selection, genotype frequencies at any locus is a simple function of allele frequencies. Testing for HWE is now a common practice in population genetics and genetic association studies of non-communicable diseases; however, it is less-regarded, or sometimes miss-interpreted, in the context of infectious diseases. In both fields, conforming to HWE assumption is usually desired. These expectations are assumed to hold for most healthy human populations, and deviations from HWE at particular markers may suggest population sub-structure, problems with genotyping or, in samples of diseased individuals, an association with the disease. Deviations from HWE are tested using simple Pearson’s χ2 test, or an equivalent log-likelihood-ratio test. The tests evaluate the degree of difference between observed genotype and allele frequencies with the frequencies that are expected if HWE assumption holds. So, statistically significant test results are suggestive of deviation from HWE assumption. Departures from HWE may suggest that allele-disease associations are biased, which should invoke thinking for the underlying reason.