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Original Paper

Free Access

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

Yang F. · Thomas D.C.

Author affiliations

Department of Preventive Medicine, University of Southern California, Los Angeles, Calif., USA

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

Related Articles for ""

Hum Hered 2011;71:209–220

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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

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