title: Quantification of the power of Hardy-Weinberg equilibrium testing to detect genotyping error.
abstract: Deviation from Hardy-Weinberg equilibrium has become an accepted test for genotyping error. While it is generally considered that testing departures from Hardy-Weinberg equilibrium to detect genotyping error is not sensitive, little has been done to quantify this sensitivity. Therefore, we have examined various models of genotyping error, including error caused by neighboring SNPs that degrade the performance of genotyping assays. We then calculated the power of chi-square goodness-of-fit tests for deviation from Hardy-Weinberg equilibrium to detect such error. We have also examined the affects of neighboring SNPs on risk estimates in the setting of case-control association studies. We modeled the power of departure from Hardy-Weinberg equilibrium as a test to detect genotyping error and quantified the effect of genotyping error on disease risk estimates. Generally, genotyping error does not generate sufficient deviation from Hardy-Weinberg equilibrium to be detected. As expected, genotyping error due to neighboring SNPs attenuates risk estimates, often drastically. For the moment, the most widely accepted method of detecting genotyping error is to confirm genotypes by sequencing and/or genotyping via a separate method. While these methods are fairly reliable, they are also costly and time consuming.
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA. dcox@hsph.harvard.edu
authors.forename: David G
authors.initials: DG
authors.lastname: Cox
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
mesh_terms: D000483:Alleles; D005838:Genotype; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D015233:Models, Statistical; D016017:Odds Ratio; D016012:Poisson Distribution; D020641:Polymorphism, Single Nucleotide; D011336:Probability; D012306:Risk