Testing for Hardy-Weinberg equilibrium in samples with related indhiduals

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 call 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 7 sample with related individuals, including large inbred pedigrees, provided that their genealogy is known. performed conditional on die pedigree structure, the QL-HW test detects departures from HW that are riot due to the genealogy. Because the computation of the QL-HW test becomes intractable for polymorphic loci in large inbred pedigrees. a simpler alternative, the GCC-HW test, is also proposed. The statistical properties of die QL-HW and GCC-HW tests are studied though 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.