A geometric interpretation of the permutation p-value and its application in eQTL studies

DOI10.1214/09-AOAS298MaRDI QIDQ993271zbMATH OpenOpenAlexFDO

Authors Fred A. Wright, Wei Sun

Publication date 10 September 2010

Published in The Annals of Applied Statistics (Search for Journal in Brave)

Full work available at URL https://arxiv.org/abs/1011.2295

zbMATH Keywords

effective number of independent testsgene expression quantitative trait loci (eQTL)permutation \(p\)-value

Mathematics Subject Classification ID

Nonparametric estimation (62G05) Applications of statistics to biology and medical sciences; meta analysis (62P10) Biochemistry, molecular biology (92C40)

Abstract: Permutation $p$-values have been widely used to assess the significance of linkage or association in genetic studies. However, the application in large-scale studies is hindered by a heavy computational burden. We propose a geometric interpretation of permutation $p$-values, and based on this geometric interpretation, we develop an efficient permutation $p$-value estimation method in the context of regression with binary predictors. An application to a study of gene expression quantitative trait loci (eQTL) shows that our method provides reliable estimates of permutation $p$-values while requiring less than 5% of the computational time compared with direct permutations. In fact, our method takes a constant time to estimate permutation $p$-values, no matter how small the $p$-value. Our method enables a study of the relationship between nominal $p$-values and permutation $p$-values in a wide range, and provides a geometric perspective on the effective number of independent tests.

Recommendations

• Fast approximation of small \(p\)-values in permutation tests by partitioning the permutations
• Efficient p-value estimation in massively parallel testing problems
• Permutation \(p\)-values should never be zero: calculating exact \(p\)-values when permutations are randomly drawn
• Accounting for Variability in the Use of Permutation Testing to Detect Quantitative Trait Loci
• Fast and accurate approximation to significance tests in genome-wide association studies

Cites work

• scientific article; zbMATH DE number 720689 (Why is no real title available?)
• scientific article; zbMATH DE number 3192509 (Why is no real title available?)
• Empirical Bayes Analysis of a Microarray Experiment
• Statistical Methods for Expression Quantitative Trait Loci (eQTL) Mapping
• The positive false discovery rate: A Bayesian interpretation and the \(q\)-value

Cited in

(3)

• Accounting for Variability in the Use of Permutation Testing to Detect Quantitative Trait Loci
• Multiple loci mapping via model-free variable selection
• A Geometric Perspective on the Power of Principal Component Association Tests in Multiple Phenotype Studies

Describes a project that uses

Uses Software

• MVTDST
• R/qtl

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