Studies that focus on identifying “template” same-phase association with genome wide levels of significance in multiple independent samples appear most likely to succeed when oligogenic genetic architecture confers large association signals in each independent sample, when the same SNP sets are studied in each, when the disease exhibits little allelic or locus heterogeneity and when there are good matches between the fine patterns of linkage disequilibrium of the samples being studied. Apparent replication “failures” using this approach could thus relate to a number of features that include associations of modest magnitude, sample-to-sample differences in fine patterns of linkage disequilibrium, different amounts of information provided by markers with population-specific differences in allele frequencies, allelic heterogeneity and locus heterogeneity.
