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Chunk #14 — METHODS — PERMUTATION TEST

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Estimation of significance thresholds for genomewide association scans.
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The 5% quantile point of the minimum P–value represents the genomewide significance threshold at this marker density. To extrapolate to complete saturation, we randomly subsampled the SNPs over a range of lower densities by equivalently subsampling the sorted P–values independently for each permutation replicate. We used a uniform grid of 100 marker densities, and at each density the 5% point of the minimum P–value was recorded. We repeated the subsampling 100 times at each density and used the mean 5% point in subsequent analysis. At low densities, the SNPs are expected to be independent; hence, according to the Bonferroni law the 5% point is inversely proportional to the number of SNPs. At high densities we expect the 5% point to converge to an asymptote, reflecting the significance threshold for the whole genome.