A direct approach to estimating false discovery rates conditional on covariates

Modern scientific studies from many diverse areas of research abound with multiple hypothesis testing concerns. The false discovery rate (FDR) is one of the most commonly used approaches for measuring and controlling error rates when performing multiple tests. Adaptive FDRs rely on an estimate of th...

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Main Authors: Simina M. Boca, Jeffrey T. Leek
Format: Article
Language:English
Published: PeerJ Inc. 2018-12-01
Series:PeerJ
Subjects:
Online Access:https://peerj.com/articles/6035.pdf
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author Simina M. Boca
Jeffrey T. Leek
author_facet Simina M. Boca
Jeffrey T. Leek
author_sort Simina M. Boca
collection DOAJ
description Modern scientific studies from many diverse areas of research abound with multiple hypothesis testing concerns. The false discovery rate (FDR) is one of the most commonly used approaches for measuring and controlling error rates when performing multiple tests. Adaptive FDRs rely on an estimate of the proportion of null hypotheses among all the hypotheses being tested. This proportion is typically estimated once for each collection of hypotheses. Here, we propose a regression framework to estimate the proportion of null hypotheses conditional on observed covariates. This may then be used as a multiplication factor with the Benjamini–Hochberg adjusted p-values, leading to a plug-in FDR estimator. We apply our method to a genome-wise association meta-analysis for body mass index. In our framework, we are able to use the sample sizes for the individual genomic loci and the minor allele frequencies as covariates. We further evaluate our approach via a number of simulation scenarios. We provide an implementation of this novel method for estimating the proportion of null hypotheses in a regression framework as part of the Bioconductor package swfdr.
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spelling doaj.art-a43f741641dc4fac83bcf452fe7f11a02023-12-03T10:58:18ZengPeerJ Inc.PeerJ2167-83592018-12-016e603510.7717/peerj.6035A direct approach to estimating false discovery rates conditional on covariatesSimina M. Boca0Jeffrey T. Leek1Innovation Center for Biomedical Informatics, Georgetown University Medical Center, Washington, D.C., USADepartment of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USAModern scientific studies from many diverse areas of research abound with multiple hypothesis testing concerns. The false discovery rate (FDR) is one of the most commonly used approaches for measuring and controlling error rates when performing multiple tests. Adaptive FDRs rely on an estimate of the proportion of null hypotheses among all the hypotheses being tested. This proportion is typically estimated once for each collection of hypotheses. Here, we propose a regression framework to estimate the proportion of null hypotheses conditional on observed covariates. This may then be used as a multiplication factor with the Benjamini–Hochberg adjusted p-values, leading to a plug-in FDR estimator. We apply our method to a genome-wise association meta-analysis for body mass index. In our framework, we are able to use the sample sizes for the individual genomic loci and the minor allele frequencies as covariates. We further evaluate our approach via a number of simulation scenarios. We provide an implementation of this novel method for estimating the proportion of null hypotheses in a regression framework as part of the Bioconductor package swfdr.https://peerj.com/articles/6035.pdfFalse discovery ratesFDR regressionAdaptive FDR
spellingShingle Simina M. Boca
Jeffrey T. Leek
A direct approach to estimating false discovery rates conditional on covariates
PeerJ
False discovery rates
FDR regression
Adaptive FDR
title A direct approach to estimating false discovery rates conditional on covariates
title_full A direct approach to estimating false discovery rates conditional on covariates
title_fullStr A direct approach to estimating false discovery rates conditional on covariates
title_full_unstemmed A direct approach to estimating false discovery rates conditional on covariates
title_short A direct approach to estimating false discovery rates conditional on covariates
title_sort direct approach to estimating false discovery rates conditional on covariates
topic False discovery rates
FDR regression
Adaptive FDR
url https://peerj.com/articles/6035.pdf
work_keys_str_mv AT siminamboca adirectapproachtoestimatingfalsediscoveryratesconditionaloncovariates
AT jeffreytleek adirectapproachtoestimatingfalsediscoveryratesconditionaloncovariates
AT siminamboca directapproachtoestimatingfalsediscoveryratesconditionaloncovariates
AT jeffreytleek directapproachtoestimatingfalsediscoveryratesconditionaloncovariates