Linkage Disequilibrium Inflates Type I Error Rates in Multipoint Linkage Analysis when Parental Genotypes Are MissingBoyles A.L. · Scott W.K. · Martin E.R. · Schmidt S. · Li Y.-J. · Ashley-Koch A. · Bass M.P. · Schmidt M. · Pericak-Vance M.A. · Speer M.C. · Hauser E.R.
Center for Human Genetics, Duke University Medical Center, Durham, N.C., USA
Elizabeth R. Hauser, PhD
Duke University Medical Center
Durham, NC 27710 (USA)
Tel. +1 919 684 2063, Fax +1 919 684 2275, E-Mail Elizabeth.Hauser@duke.edu
Do you have an account?
Objectives: Describe the inflation in nonparametric multipoint LOD scores due to inter-marker linkage disequilibrium (LD) across many markers with varied allele frequencies. Method: Using simulated two-generation families with and without parents, we conducted nonparametric multipoint linkage analysis with 2 to 10 markers with minor allele frequencies (MAF) of 0.5 and 0.1. Results: Misspecification of population haplotype frequencies by assuming linkage equilibrium caused inflated multipoint LOD scores due to inter-marker LD when parental genotypes were not included. Inflation increased as more markers in LD were included and decreased as markers in equilibrium were added. When marker allele frequencies were unequal, the r2 measure of LD was a better predictor of inflation than D′. Conclusion: This observation strongly supports the evaluation of LD in multipoint linkage analyses, and further suggests that unaccounted for LD may be suspected when two-point and multipoint linkage analyses show a marked disparity in regions with elevated r2 measures of LD. Given the increasing popularity of high-density genome-wide SNP screens, inter-marker LD should be a concern in future linkage studies.
© 2005 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.