- Candidate gene associations
- Cochran-Armitage trend test
- MAX test
- Maximin efficiency robust test
- Power approximation
- Sample size
The Cochran-Armitage trend test is commonly used as a genotype-based test for candidate gene association. Corresponding to each underlying genetic model there is a particular set of scores assigned to the genotypes that maximizes its power. When the variance of the test statistic is known, the formulas for approximate power and associated sample size are readily obtained. In practice, however, the variance of the test statistic needs to be estimated. We present formulas for the required sample size to achieve a prespecified power that account for the need to estimate the variance of the test statistic. When the underlying genetic model is unknown one can incur a substantial loss of power when a test suitable for one mode of inheritance is used where another mode is the true one. Thus, tests having good power properties relative to the optimal tests for each model are useful. These tests are called efficiency robust and we study two of them: the maximin efficiency robust test is a linear combination of the standardized optimal tests that has high efficiency and the MAX test, the maximum of the standardized optimal tests. Simulation results of the robustness of these two tests indicate that the more computationally involved MAX test is preferable.
Copyright © 2002 S. Karger AG, Basel
- Sasieni PD: From genotypes to genes: Doubling the sample size. Biometrics 1997;53:1253–1261.
- Cohcran WG: Some methods for strengthening the common chi-squared tests. Biometrics 1954;10:417–451.
- Armitage P: Tests for linear trends in proportions and frequencies. Biometrics 1955;11:375–386.
- Tarone RE, Gart JJ: On the robustness of combined tests for trends in proportions. J Am Stat Assoc 1980;75:110–116.
- Slager SL, Schaid DJ: Case-control studies of genetic markers: Power and sample size approximations for Armitage’s test for trend. Hum Hered 2001;52:149–153.
- Gastwirth JL: The use of maximin efficiency robust tests in combining contingency tables and survival analysis. J Am Stat Assoc 1985;80:380–384.
- Podgor MJ, Gastwirth JL, Mehta CR: Efficiency robust tests of independence in contingency tables with ordered classifications. Stat Med 1996;15:2095–2105.
- Whittemore AS, Tu I-P: Simple, robust linkage tests for affected sibs. Am J Hum Genet 1998;62:1228–1242.
- Freidlin B, Podgor MJ, Gastwirth JL: Efficiency robust tests for survival or ordered categorical data. Biometrics 1999;55:883–886.
- Shih M, Whittemore AS: Allele-sharing among affected relatives: Non-parametric methods for identifying genes. Stat Methods Med Res 2001;10:27–55.
- Shahbazi M, Pravica P, Nasreen N, Fakhoury H, Fryer AA, Strange RC, Hutchinson PE, Osborne JE, Lear JT, Smith AG, Hutchinson IV: Association between functional polymorphism in EGF gene and malignant melanoma. Lancet 2002;359:397–401.
- Vogel F, Motulsky AG: Human Genetics: Problems and Approaches, ed 3. New York, Springer, 1997.
- Ott J: Analysis of Human Genetic Linkage, ed 3. Baltimore, JHU Press, 1999.
Biometric Research Branch
National Cancer Institute
MSC 7434, Bethesda, MD 20892 (USA)
Received: January 31, 2002
Accepted: March 28, 2002
Revision received: March 22, 2002
Published online: June 11, 2009
Number of Print Pages : 7
Number of Figures : 0, Number of Tables : 8, Number of References : 13
Human Heredity (International Journal of Human and Medical Genetics)
Founded 1950 as Acta Genetica et Statistica Medica by Gunnar Dahlberg; Continued by M. Hauge (1965–1983)
Vol. 53, No. 3, Year 2002 (Cover Date: Released July 2002)
Journal Editor: J. Ott, New York, N.Y.
ISSN: 0001–5652 (Print), eISSN: 1423–0062 (Online)
For additional information: http://www.karger.ch/journals/hhe
Copyright / Drug Dosage / Disclaimer
Copyright: 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 or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
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 goverment 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.