Our data indicate that this approach may be a useful adjunct to conventional analysis and that loci identified as highly significant should be considered for follow up. There are two important caveats. First, susceptibility genes that influence both the test disease and one or more of the diseases included in the reference group will cause loss of power. Second, a ‘mirror-image’ effect could occur whereby a strong association within the expanded reference sample (for example, HLA in autoimmune diseases) causes spurious association with the opposite allele in the test disease. Thus, a positive association using an expanded reference group must be interpreted within the context of association findings in the diseases included within the reference group.
