Login to MyKarger

New to MyKarger? Click here to sign up.

Login with Facebook

Forgot Password? Reset your password

Authors, Editors, Reviewers

For Manuscript Submission, Check or Review Login please go to Submission Websites List.

Submission Websites List

Institutional Login (Shibboleth)

For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.

Table of Contents
Vol. 71, No. 4, 2011
Issue release date: September 2011
Section title: Original Paper
Free Access
Hum Hered 2011;71:209–220

Two-Stage Design of Sequencing Studies for Testing Association with Rare Variants

Yang F. · Thomas D.C.
Department of Preventive Medicine, University of Southern California, Los Angeles, Calif., USA
email Corresponding Author

Duncan C. Thomas

Department of Preventive Medicine

University of Southern California

Los Angeles, CA 90089-9011 (USA)

Tel. +1 323 442 1218, E-Mail dthomas@usc.edu

Do you have an account?

Login Information

Contact Information

I have read the Karger Terms and Conditions and agree.


Multiple rare variants have been suggested as accounting for some of the associations with common single nucleotide polymorphisms identified in genome-wide association studies or possibly some of the as yet undiscovered heritability. We consider the power of various approaches to designing substudies aimed at using next-generation sequencing technologies to discover novel variants and to select some subsets that are possibly causal for genotyping in the original case-control study and testing for association using various weighted sum indices. We find that the selection of variants based on the statistical significance of the case-control difference in the subsample yields good power for testing rare variant indices in the main study, and that multivariate models including both the summary index of rare variants and the associated common single nucleotide polymorphisms can distinguish which is the causal factor. By simulation, we explore the effects of varying the size of the discovery subsample, choice of index, and true causal model.

© 2011 S. Karger AG, Basel

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: December 01, 2010
Accepted: March 31, 2011
Published online: July 02, 2011
Issue release date: September 2011

Number of Print Pages: 12
Number of Figures: 2
Number of Tables: 7

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

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