On an extended interpretation of linkage disequilibrium in genetic case-control association studies.

We are concerned with statistical inference for 2 × C × K contingency tables in the context of genetic case-control association studies. Multivariate methods based on asymptotic Gaussianity of vectors of test statistics require information about the asymptotic correlation structure among these test statistics under the global null hypothesis. In the case of C=2, we show that for a wide variety of test statistics this asymptotic correlation structure is given by the standardized linkage disequilibrium matrix of the K loci under investigation. Three popular choices of test statistics are discussed for illustration. In the case of C=3, the standardized composite linkage disequilibrium matrix is the limiting correlation matrix of the K locus-specific Cochran-Armitage trend test statistics.