There are a number of important limitations that come from these samples, these analyses, and from the application of this approach to these datasets. The two distinct null hypotheses both require careful thinking about linkage disequilibrium, since it is easy to confuse data and analyses that bear on linkage disequilibrium among markers that display case vs control differences in single samples, the chromosomal regions that such markers label, and the chromosomal regions labeled by such sets of markers in multiple independent samples. Especial difficulties in clarity may arise since we anticipate true positive results that combine differences between cases and controls that are based on linkage disequilibrium among markers that display case vs control association with disease and between these markers and the functional allelic variants that provide the variation in gene function that influences phenotype. Without dissecting these differences, it is easy to come to the incorrect conclusion that the method described herein is only detecting the linkage disequilibrium structure and not disease association.
