Hardy Weinberg Equilibrium Disturbances in Case-ControlStudies Lead to Non-Conclusive Results

摘要

Recently, it has been proposed the association of a common deletion affecting toll-like receptor 2 promoter (-196to -177) to type 2 diabetes mellitus risk. However, genotyping results show a significant deviation from theHardyWeinberg Equilibrium (HWE). The law of Hardy-Weinberg shows that for an autosomal biallelic marker with allelefrequencies fA=p and fa=q, the proportion of subjects with genotypes AA, Aa, and aa should follow the following: fAA=p2, fAa=2pq, and faa=q2. Departure from HWE or Hardy-Weinberg Disequilibrium (HWD) in a human control population canbe caused by natural factors such as selective pressure against a certain genotype. However their prevalence is scarceand magnitude of effect over the HWE are small. Other factors such as inbreeding caused by consanguinity, populationstratification, or technical problems in genotyping are more usual. Nevertheless, if the control population follows aperfect HWE, the presence HWD among patients might be explained by the genetic association and evidencing a reallink between the locus and the trait under study. However, HWD affecting both cases and controls, such as the onereported might be explained by one of the aforementioned issues.