A Generalized Sequential Bonferroni Procedure Using Smoothed Weights for Genome-Wide Association Studies Incorporating Information on Hardy-Weinberg Disequilibrium among CasesGao 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
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
Department of Biostatistics, Virginia Commonwealth University
PO Box 980032
Richmond, VA 23298-0032 (USA)
Tel. +1 804 827 2775, E-Mail email@example.com
Do you have an account?
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
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.