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Original Paper

Free Access

Practical Considerations for Dividing Data into Subsets Prior to PPL Analysis

Govil M.a · Vieland V.J.b

Author affiliations

aDepartment of Oral Biology and Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pa., bBattelle Center of Mathematical Medicine, The Research Institute at Nationwide Children’s Hospital and The Ohio State University, Columbus, Ohio, USA

Corresponding Author

Manika Govil

Suite 500 Cellomics/Bridgeside Point

100 Technology Drive

Pittsburgh, PA 15219 (USA)

Tel. +1 412 648 9204, Fax +1 412 648 8779, E-Mail govil@pitt.edu

Related Articles for ""

Hum Hered 2008;66:223–237

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Objective: The PPL, a class of statistics for complex trait genetic mapping in humans, utilizes Bayesian sequential updating to accumulate evidence for or against linkage across potentially heterogeneous data (sub)sets. Here, we systematically explore the relative efficacy of alternative subsetting approaches for purposes of PPL calculation. Methods: We simulated genotypes for three pedigree sets (sib pairs; 2–3 generations; ≧4 generations) based on families from an ongoing study. For each pedigree set, 100 replicates were generated under different levels of heterogeneity (1000 under ‘no linkage’). Within each replicate, updating was performed across subsets defined randomly (RAND2, RAND4), by true (TRUE) linkage status, with a realistic (REAL) classification, by individual pedigree (PED), or without any subsetting (NONE). Results: Under ‘linkage’, REAL yields larger PPLs compared to NONE, RAND2, RAND4, or PED. Under ‘no linkage’, RAND2, RAND4 and PED yield PPLs close to NONE. Conclusions: We have examined the impact of different subsetting strategies on the sampling behavior of the PPL. Our results underscore the utility of finding variables that can help delineate more homogeneous data subsets and demonstrate that, once such variables are found, sequential updating can be highly beneficial in the presence of appreciable heterogeneity at a linked locus, without inflation at an unlinked locus.

© 2008 S. Karger AG, Basel

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: September 24, 2007
Accepted: November 16, 2007
Published online: July 09, 2008
Issue release date: October 2008

Number of Print Pages: 15
Number of Figures: 5
Number of Tables: 6

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

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

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