Checking for Hardy-Weinberg Equilibrium (HWE) is one final step in the quality control analysis of markers in GWAS data. Under Hardy-Weinberg assumptions, allele and genotype frequencies can be estimated from one generation to the next. Departure from this equilibrium can be indicative of potential genotyping errors, population stratification, or even actual association to the trait under study [46]. UNIT 1.18 contains a very detailed description of the key principles and assumptions of HWE and how HWE is tested and applied in genetic association studies [47]. HWE can be assessed using the --hardy option in PLINK. While departure from HWE can indicate potential genotyping error, disequilibrium can also result from a true association. It has been consistently noted that many more SNPs are out of HWE at any given significance threshold than would be expected by chance. SNPs severely out of HWE should therefore not be eliminated from the analysis, but flagged for further analysis after the association analyses are performed. Databases such as MySQL (see Table 1) can be very useful for joining association statistics with HWE statistics for easy
