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Background  Large-scale genetic association studies can test hundreds of thousands of genetic markers for association with a trait. Since the genetic markers may be correlated, a Bonferroni correction is typically too stringent a correction for multiple testing. Permutation testing is a standard statistical technique for determining statistical significance when performing multiple correlated tests for genetic association. However, permutation testing for large-scale genetic association studies is computationally demanding and calls for optimized algorithms and software. PRESTO is a new software package for genetic association studies that performs fast computation of multiple-testing adjusted P-values via permutation of the trait.    Results  PRESTO is an order of magnitude faster than other existing permutation testing software, and can analyze a large genome-wide association study (500 K markers, 5 K individuals, 1 K permutations) in approximately one hour of computing time. PRESTO has several unique features that are useful in a wide range of studies: it reports empirical null distributions for the top-ranked statistics (i.e. order statistics), it performs user-specified combinations of allelic and genotypic tests, it performs stratified analysis when sampled individuals are from multiple populations and each individual's population of origin is specified, and it determines significance levels for one and two-stage genotyping designs. PRESTO is designed for case-control studies, but can also be applied to trio data (parents and affected offspring) if transmitted parental alleles are coded as case alleles and untransmitted parental alleles are coded as control alleles.    Conclusion  PRESTO is a platform-independent software package that performs fast and flexible permutation testing for genetic association studies. The PRESTO executable file, Java source code, example data, and documentation are freely available at   .

bmc bioinformatics

PRESTO: Rapid calculation of order statistic distributions and multiple-testing adjusted P-values via permutation for one and two-stage genetic association studies