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Original Paper

Free Access

A Generalized Sequential Bonferroni Procedure Using Smoothed Weights for Genome-Wide Association Studies Incorporating Information on Hardy-Weinberg Disequilibrium among Cases

Gao G.a · Kang G.b · Wang J.a · Chen W.a · Qin H.c · Jiang B.d · Li Q.e · Sun C.a · Liu N.d · Archer K.J.a · Allison D.B.d

Author affiliations

aDepartment of Biostatistics, Virginia Commonwealth University, Richmond, Va., bDepartment of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pa., cDepartment of Biostatistics and Epidemiology, Case Western Reserve University, Cleveland, Ohio, and dDepartment of Biostatistics, University of Alabama at Birmingham, Birmingham, Ala., USA; eAcademy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing, PR China

Corresponding Author

Guimin Gao

Department of Biostatistics, Virginia Commonwealth University

PO Box 980032

Richmond, VA 23298-0032 (USA)

Tel. +1 804 827 2775, E-Mail ggao3@vcu.edu

Related Articles for ""

Hum Hered 2012;73:1–13

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Background/Objectives: For genome-wide association studies (GWAS) with case-control designs, one of the most widely used association tests is the Cochran-Armitage (CA) trend test assuming an additive mode of inheritance. The CA trend test often has higher power than other association tests under additive and multiplicative disease models. However, it can have very low power under a recessive disease model in GWAS. Although tests (such as MAX3) robust to different genetic models have been developed, they often have relatively lower power than the CA trend test under additive and multiplicative models. The goal of this study is to propose an efficient method that not only has higher power than the CA trend test under dominant and recessive models but also maintains the power of the CA trend test under additive and multiplicative models. Methods: We employed the generalized sequential Bonferroni (GSB) procedure of Holm to incorporate information from a Hardy-Weinberg disequilibrium (HWD) test into the CA trend test based on estimating weights from the p values of the HWD test. We proposed to smooth the weights to reduce possible noise. Results and Conclusions: Results from extensive simulation studies showed that the proposed GSB procedure can achieve the goal described above.

© 2011 S. Karger AG, Basel

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: June 15, 2011
Accepted: September 07, 2011
Published online: December 30, 2011
Issue release date: March 2012

Number of Print Pages: 13
Number of Figures: 0
Number of Tables: 5

ISSN: 0001-5652 (Print)
eISSN: 1423-0062 (Online)

For additional information: http://www.karger.com/HHE

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