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This article is part of the supplement: Genetic Analysis Workshop 17: Unraveling Human Exome Data

Open Access Proceedings

Gene-based Higher Criticism methods for large-scale exonic single-nucleotide polymorphism data

Shiquan He and Zheyang Wu*

Author Affiliations

Department of Mathematical Sciences, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA 01609-2280, USA

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BMC Proceedings 2011, 5(Suppl 9):S65  doi:10.1186/1753-6561-5-S9-S65

Published: 29 November 2011

Abstract

In genome-wide association studies, gene-based methods measure potential joint genetic effects of loci within genes and are promising for detecting causative genetic variations. Following recent theoretical research in statistical multiple-hypothesis testing, we propose to adapt the Higher Criticism procedures to develop novel gene-based methods that use the information of linkage disequilibrium for detecting weak and sparse genetic signals. With the large-scale exonic single-nucleotide polymorphism data from Genetic Analysis Workshop 17, we show that the new Higher-Criticism-type gene-based methods have higher statistical power to detect causative genes than the minimal P-value method, ridge regression, and the prototypes of Higher Criticism do.