Population stratification, not genotype error, causes some SNPs to depart from Hardy-Weinberg Equilibrium

Abstract

Large scale whole genome scans generate massive amounts of genotype data. It is essential to check genotype integrity and identify genotype errors prior to association analysis. Departure from Hardy-Weinberg Equilibrium has been adopted as one of the main methods to identify genotype errors. However population stratification also causes departure from Hardy-Weinberg Equilibrium, which is a disadvantage of this approach. This study used 2 sets of SNP genotypes to show that after basic editing using Call Rate and minor allele frequency, up to 13% of SNPs departed from Hardy-Weinberg Equilibrium (HWD) and about one third of these HWD SNPs could be falsely identified as genotype errors, were attributable to population subdivision (eg herd of origin, cohort) for one dataset and corresponding numbers for the second dataset are 21% and 16%, respectively. This approach can avoid improper culling of a considerable proportion of SNPs.