Deviations from hardy-weinberg equilibrium in parental and unaffected sibling genotype data

Background: Genotyping error can increase both type I and II errors. In order to elucidate potential genotyping errors, data quality control often includes testing genotype data for deviations from Hardy-Weinberg Equilibrium (HWE).

Methods: The Hardy-Weinberg Disequilibrium (HWD) coefficient and the ability to reject the null hypothesis of HWE were calculated analytically for genotype data from parents and unaffected siblings of affected probands.

Results: Genotype data from parents and unaffected siblings display deviations from HWE when functional or markers in LD with functional locus are tested. For the parental genotype data all deviations from HWE are negative, indicating an excess of heterozygous genotypes with the strongest deviations from HWE observed for the multiplicative model. In contrast, for affected proband genotype data, there is no deviation from HWE under the multiplicative model and the deviations from HWE for the recessive model are positive. For the unaffected sibling data, patterns of deviation from HWE are similar to those observed in the proband data with the exception of the multiplicative model where the HWD coefficient although close to 0 can be either positive or negative depending on the allele frequency.

Conclusion: Deviations from HWE in parental and unaffected sibling genotype data could be due to an association with the functional locus. However these deviations for genotypic relative risk < or =2.0 are not large and therefore the power to detect them is usually low. Testing for deviations from HWE in parental and unaffected sibling genotype data is still beneficial for quality control even though functional loci, in parental and unaffected sibling genotype data, can produce an association signal.