Increased Efficiency of Case-Control Association Analysis by Using Allele-Sharing and Covariate InformationSchmidt S. · Schmidt M.A. · Qin X. · Martin E.R. · Hauser E.R.
Center for Human Genetics, Duke University Medical Center, Durham, N.C., USA
Silke Schmidt, PhD
Center for Human Genetics, Duke University Medical Center
Durham, NC 27710 (USA)
Tel. +1 919 684 0624, Fax +1 919 684 0925, E-Mail firstname.lastname@example.org
Do you have an account?
Objective: We compared the efficiency of case selection strategies for following up a genome-wide linkage screen of multiplex families. We simulated datasets under three models by which continuous environmental or clinical covariates may contribute to disease risk or linkage heterogeneity: (i) a quantitative trait locus (QTL) underlying a continuous disease risk factor, (ii) a gene-environment interaction model, (iii) a heterogeneity model defined by distinct covariate distributions in linked and unlinked families. Methods: Marker genotypes and covariate values were generated for affected sibling pair (ASP) families, according to the three models above. We evaluated two case selection strategies relative to a reference design, which compared all family probands to a sample of unrelated controls (‘all’). The first strategy ignored covariates and selected probands from families with NPL scores ≧0 (‘linked best’). The second strategy selected probands from families identified by an ordered subset analysis (OSA), which utilizes family-specific linkage and covariate information. Results: The ‘linked best’ design provided power very similar to the ‘all’ design under all three models. Under some QTL and heterogeneity models, the OSA design was both most powerful and most efficient. Conclusions: Incorporating allele sharing and covariate information from ASP families into a case-control study design can increase power and reduce genotyping cost.
© 2007 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 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 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.