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Abstract:
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Permutation p-value has been widely used to access the significance of linkage score in genetic studies. However its application in large-scale linkage studies is hindered by its heavy computational burden. In this study, we propose a method to estimate permutation p-values for linkage studies based on a geometric interpretation of permutation p-values. Suppose a quantitative/qualitative trait and p genetic markers are studied in n individuals. The p marker genotype profiles are p points in the n dimensional space. Permutation p-value is related with the space occupied by the p points. We define a new concept, "effective volume," which is the volume occupied by the observed genotype profiles according to the cutoff of linkage score, and develop an efficient algorithm to estimate the "effective volume," hence the permutation p-value.
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