Testing for Hardy-Weinberg equilibrium in samples with related individuals.
When the classical chi(2) goodness-of-fit test for Hardy-Weinberg (HW) equilibrium is used on samples with related individuals, the type I error can be greatly inflated. In particular the test is inappropriate in population isolates where the individuals are related through multiple lines of descent. In this article, we propose a new test for HW (the QL-HW test) suitable for any sample with related individuals, including large inbred pedigrees, provided that their genealogy is known. Performed conditional on the pedigree structure, the QL-HW test detects departures from HW that are not due to the genealogy. Because the computation of the QL-HW test becomes intractable for very polymorphic loci in large inbred pedigrees, a simpler alternative, the GCC-HW test, is also proposed. The statistical properties of the QL-HW and GCC-HW tests are studied through simulations considering a sample of independent nuclear families, a sample of extended outbred genealogies, and samples from the Hutterite population, a North American highly inbred isolate. Finally, the method is used to test a set of 143 biallelic markers spanning 82 genes in this latter population.
Bourgain
Catherine
C
INSERM U535, 94817 Villejuif Cedex, France. bourgain@vjf.inserm.fr <bourgain@vjf.inserm.fr>
Abney
Mark
M
Schneider
Daniel
D
Ober
Carole
C
McPeek
Mary Sara
MS
D016009:Chi-Square Distribution; D003627:Data Interpretation, Statistical; D008957:Models, Genetic