A test for linkage and association in general pedigrees

Abstract

Family-based tests of linkage disequilibrium are usually based on nuclear family data including affected individuals and their parents or their unaffected siblings. A problem with these tests is that they are not valid tests of association when data from related nuclear families from larger pedigrees are used. One way to ensure validity when testing for association is to select a single nuclear family from each extended pedigree in the sample. When data are available for larger pedigrees, it would be desirable to have a valid test of linkage disequilibrium that can use all potentially informative data. In this paper we present such a test: the Pedigree Disequilibrium Test (PDT). The PDT can use data from related nuclear families from extended pedigrees and remains valid when there is population substructure. Power simulations demonstrate that, when extended pedigree data are available, gains in power can be obtained by using the PDT rather than existing methods that only use a subset of the data. The PDT can also be more powerful than current methods when the data consist of a sample of independent nuclear families or sibships.