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Original Paper

Free Access

Assessing Genuine Parents-Offspring Trios for Genetic Association Studies

Teo Y.Y.a, · Fry A.E.a, · Sanjoaquin M.A.a · Pederson B.c · Small K.S.a · Rockett K.A.a · Kwiatkowski D.P.a, b · Clark T.G.a, b

Author affiliations

aWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, and bWellcome Trust Sanger Institute, Hinxton, Cambridge, UK; cUniversity of Iowa, Iowa City, Iowa, USA

Corresponding Author

Yik Y. Teo, DPil

Wellcome Trust Centre for Human Genetics

Roosevelt Drive

Oxford OX3 7BN (UK)

Tel. +44 1865 287 712; Fax +44 1865 287 501, E-Mail teo@well.ox.ac.uk

Related Articles for ""

Hum Hered 2009;67:26–37

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Objectives: Family-based association tests such as the transmission disequilibrium test (TDT) are dependent on the successful ascertainment of true nuclear family trios. Relationship misspecification inevitably occurs in a proportion of trios collected for genotyping which undetected can lead to a loss of power and increased Type I error due to biases in over-transmission of common alleles. Here, we introduce a method for evaluating the authenticity of nuclear family trios. Methods: Operating in a Bayesian framework, our approach assesses the extent of pedigree inconsistent genotype configurations in the presence of genotyping errors. Unlike other approaches, our method: (i) utilizes information from three individuals collectively (the whole trio) rather than consider two independent pairwise relationships; (ii) down-weighs SNPs with poor performance; (iii) does not require the user to pre-define a rate of genotyping error, which is often unknown to the user and seldom fixed across the different SNPs considered which available methods unrealistically assumed. Results: Simulation studies and comparisons with a real set of data showed that our approach is more likely to correctly identify the presence of true and misspecified trios compared to available software, accurately infers the extent of relationship misspecification in a trio and accurately estimates the genotyping error rates. Conclusions: Assessing relationship misspecification depends on the fidelity of the genotype data used. Available algorithms are not optimised for genotyping technology with varying rates of errors across the markers. Through our comparison studies, our approach is shown to outperform available methods for assessing relationship misspecifications.

© 2008 S. Karger AG, Basel


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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: October 18, 2007
Accepted: December 20, 2007
Published online: October 17, 2008
Issue release date: November 2008

Number of Print Pages: 12
Number of Figures: 4
Number of Tables: 4

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

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