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

DOI10.1214/09-AOAS298zbMATH Open1194.62121arXiv1011.2295OpenAlexW2015919706MaRDI QIDQ993271FDOQ993271

Authors: Fred A. Wright, Wei Sun 

Publication date: 10 September 2010

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

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.

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

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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)

Cites Work

• Title not available (Why is that?)
• Statistical Methods for Expression Quantitative Trait Loci (eQTL) Mapping
• Empirical Bayes Analysis of a Microarray Experiment
• The positive false discovery rate: A Bayesian interpretation and the \(q\)-value
• Title not available (Why is that?)

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

Uses Software

• R/qtl
• MVTDST

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