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Challenging False Discovery Rate: A Partition Test Based on p Values in Human Case-Control Association Studies
Ott, Jurg1; Liu, Zhe2; Shen, Yuanyuan3; Ott, J (reprint author), Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, 4A Datun Rd, Beijing 100101, Peoples R China.
2012
Source PublicationHUMAN HEREDITY
ISSN0001-5652
SubtypeArticle
Volume74Issue:1Pages:45-50
Contribution Rank1
AbstractBackground/Aims: We consider the situation that multiple genetic variants are underlying a heritable trait and assume that each contributes to the trait only to a small degree. The aim is to develop a statistical test for disease association of these multiple variants. Methods: We expect that p values resulting from a genome-wide case-control association analysis will fall into two classes: those reflecting true association and those occurring randomly in the interval from 0 to 1. We develop a partition test to find the set of smallest p values deviating most from the number of p values expected under randomness. Results: Power calculations demonstrate the superiority of our partition test over conventional SNP-by-SNP analyses. Applications of the partition test to six published datasets show that our test is particularly suitable when multiple SNPs appear to contribute to a trait, and furnished more significant results than a well-known procedure to estimate the false discovery rate. Conclusions: Our partition test also furnishes an estimate of the number of functional SNPs underlying disease and can be highly significant, while single-locus tests may be far from significant. Copyright (C) 2012 S. Karger AG, Basel
KeywordMultilocus analysis Case-control association test False discovery rate Multiple testing
Subject AreaMedical Psychology
Indexed BySCI
Language英语
Funding OrganizationChina NSFC [30730057] ; Rockefeller University from the Albert Einstein College of Medicine
Project Intro.Support from China NSFC grant No. 30730057 is gratefully acknowledged. This study used data from the SNP Database at the NINDS Human Genetics Resource Center DNA and Cell Line Repository (http://ccr.coriell.org/ninds), as well as clinical data. The original genotyping was performed in the laboratories of Drs. Singleton and Hardy, (NIA, LNG), Bethesda, Md., USA. Funding support for development of a novel analysis methods was provided by the Rockefeller University, based on a subcontract from the Albert Einstein College of Medicine, and the genotyping of samples was provided through the Genetic Association Information Network (GAIN). The schizophrenia dataset used for the analyses described in this study was obtained from the database of Genotype and Phenotype (dbGaP) found at http://www.ncbi.nlm.nih.gov/gap. We thank Dr. P.K. Gregersen for allowing us to use his RA dataset for this study.
WOS IDWOS:000311045000006
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Cited Times:4[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/11435
Collection中国科学院心理健康重点实验室
Corresponding AuthorOtt, J (reprint author), Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, 4A Datun Rd, Beijing 100101, Peoples R China.
Affiliation1.Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Beijing 100101, Peoples R China
2.Univ Chicago, Dept Stat, Chicago, IL 60637 USA
3.Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA
First Author AffilicationKey Laboratory of Mental Health, CAS
Recommended Citation
GB/T 7714
Ott, Jurg,Liu, Zhe,Shen, Yuanyuan,et al. Challenging False Discovery Rate: A Partition Test Based on p Values in Human Case-Control Association Studies[J]. HUMAN HEREDITY,2012,74(1):45-50.
APA Ott, Jurg,Liu, Zhe,Shen, Yuanyuan,&Ott, J .(2012).Challenging False Discovery Rate: A Partition Test Based on p Values in Human Case-Control Association Studies.HUMAN HEREDITY,74(1),45-50.
MLA Ott, Jurg,et al."Challenging False Discovery Rate: A Partition Test Based on p Values in Human Case-Control Association Studies".HUMAN HEREDITY 74.1(2012):45-50.
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