Clustering of positive results in the same gene in each of several independent samples is much less likely to represent purely stochastic effects than observations made in any single sample. Such clustering in multiple samples is more likely to reflect true differences related to the phenotype of interest, eg dependence on addictive substances. However, it is important to emphasize again that these criteria are aimed at identification of genes, rather than precise definition of exact disease-associated haplotypes. We thus allow the phase of association to differ between samples at this level of analysis. Detailed studies of the phase of association can provide a very valuable fine mapping tool to allow identification of the exact pathogenic haplotype [131].
