Testing for Hardy-Weinberg equilibrium in samples with related individuals

Genetics. 2004 Dec;168(4):2349-61. doi: 10.1534/genetics.104.031617. Epub 2004 Sep 15.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chi-Square Distribution
  • Data Interpretation, Statistical*
  • Models, Genetic*