When λ = 1.5 (which would be common if patients and controls came from different European countries) (Table 2), the original p-value must be approximately three times lower than 0.05. For geographically distant samples, the necessary reduction may be by a factor of up to 500, as would be the case with Kuusamo and Southern Italy. Interestingly, λ values with respect to other samples are smaller for CEU (originating mostly from Northern Germany, Netherlands and Belgia [12]) than for Northern Germany. This is probably due to the higher genetic variability in the CEU sample, ancestry of which is from a mixture of several different populations and therefore the CEU sample is a better reference for European population than a single population. It should be pointed out that any adjustment for stratification does inflate the multiple testing correction so that, if genetically distant case and control samples are compared in an association study, the genome-wide significance threshold in some cases would even be as low as p<1×10−10.
