A Note on Exact Tests of Hardy-Weinberg Equilibrium.
Wigginton JE, Cutler DJ and Abecasis GR
Am J Hum Genet (2005) 76: 887-93
Deviations from Hardy-Weinberg equilibrium (HWE) can indicate inbreeding, population stratification, and even problems in genotyping. In samples of affected individuals,
these deviations can also
provide evidence for association. Tests of HWE are commonly performed using a simple goodness-of-fit test. We show that this test can have inflated type I error rates,
even in relatively large
samples (e.g., samples of 1,000 individuals that include 100 copies of the minor allele). On the basis of previous work, we describe exact tests of HWE together with
efficient computational methods for
their implementation. Our methods adequately control type I error in large and small samples and are computationally efficient. They have been implemented in freely
available code that will be useful
for quality assessment of genotype data and for the detection of genetic association or population stratification in very large data sets.