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Rapid and robust association mapping of expression quantitative trait loci

We applied a simple and efficient two-step method to analyze a family-based association study of gene expression quantitative trait loci (eQTL) in a mixed model framework. This two-step method produces very similar results to the full mixed model method, with our method being significantly faster th...

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Autores principales: Lam, Alex C, Schouten, Michael, Aulchenko, Yurii S, Haley, Chris S, de Koning, Dirk-Jan
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2367564/
https://www.ncbi.nlm.nih.gov/pubmed/18466488
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author Lam, Alex C
Schouten, Michael
Aulchenko, Yurii S
Haley, Chris S
de Koning, Dirk-Jan
author_facet Lam, Alex C
Schouten, Michael
Aulchenko, Yurii S
Haley, Chris S
de Koning, Dirk-Jan
author_sort Lam, Alex C
collection PubMed
description We applied a simple and efficient two-step method to analyze a family-based association study of gene expression quantitative trait loci (eQTL) in a mixed model framework. This two-step method produces very similar results to the full mixed model method, with our method being significantly faster than the full model. Using the Genetic Analysis Workshop 15 (GAW15) Problem 1 data, we demonstrated the value of data filtering for reducing the number of tests and controlling the number of false positives. Specifically, we showed that removing non-expressed genes by filtering on expression variability effectively reduced the number of tests by nearly 50%. Furthermore, we demonstrated that filtering on genotype counts substantially reduced spurious detection. Finally, we restricted our analysis to the markers and transcripts that were closely located. We found five times more signals in close proximity (cis-) to transcripts than in our genome-wide analysis. Our results suggest that careful pre-filtering and partitioning of data are crucial for controlling false positives and allowing detection of genuine effects in genetic analysis of gene expression.
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spelling pubmed-23675642008-05-06 Rapid and robust association mapping of expression quantitative trait loci Lam, Alex C Schouten, Michael Aulchenko, Yurii S Haley, Chris S de Koning, Dirk-Jan BMC Proc Proceedings We applied a simple and efficient two-step method to analyze a family-based association study of gene expression quantitative trait loci (eQTL) in a mixed model framework. This two-step method produces very similar results to the full mixed model method, with our method being significantly faster than the full model. Using the Genetic Analysis Workshop 15 (GAW15) Problem 1 data, we demonstrated the value of data filtering for reducing the number of tests and controlling the number of false positives. Specifically, we showed that removing non-expressed genes by filtering on expression variability effectively reduced the number of tests by nearly 50%. Furthermore, we demonstrated that filtering on genotype counts substantially reduced spurious detection. Finally, we restricted our analysis to the markers and transcripts that were closely located. We found five times more signals in close proximity (cis-) to transcripts than in our genome-wide analysis. Our results suggest that careful pre-filtering and partitioning of data are crucial for controlling false positives and allowing detection of genuine effects in genetic analysis of gene expression. BioMed Central 2007-12-18 /pmc/articles/PMC2367564/ /pubmed/18466488 Text en Copyright © 2007 Lam et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Proceedings
Lam, Alex C
Schouten, Michael
Aulchenko, Yurii S
Haley, Chris S
de Koning, Dirk-Jan
Rapid and robust association mapping of expression quantitative trait loci
title Rapid and robust association mapping of expression quantitative trait loci
title_full Rapid and robust association mapping of expression quantitative trait loci
title_fullStr Rapid and robust association mapping of expression quantitative trait loci
title_full_unstemmed Rapid and robust association mapping of expression quantitative trait loci
title_short Rapid and robust association mapping of expression quantitative trait loci
title_sort rapid and robust association mapping of expression quantitative trait loci
topic Proceedings
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2367564/
https://www.ncbi.nlm.nih.gov/pubmed/18466488
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