Cargando…

A combined strategy for quantitative trait loci detection by genome-wide association

BACKGROUND: We applied a range of genome-wide association (GWA) methods to map quantitative trait loci (QTL) in the simulated dataset provided by the 12(th )QTLMAS workshop in order to derive an effective strategy. RESULTS: A variance component linkage analysis revealed QTLs but with low resolution....

Descripción completa

Detalles Bibliográficos
Autores principales: Lam, Alex C, Powell, Joseph, Wei, Wen-Hua, de Koning, Dirk-Jan, Haley, Chris S
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654500/
https://www.ncbi.nlm.nih.gov/pubmed/19278545
_version_ 1782165376234160128
author Lam, Alex C
Powell, Joseph
Wei, Wen-Hua
de Koning, Dirk-Jan
Haley, Chris S
author_facet Lam, Alex C
Powell, Joseph
Wei, Wen-Hua
de Koning, Dirk-Jan
Haley, Chris S
author_sort Lam, Alex C
collection PubMed
description BACKGROUND: We applied a range of genome-wide association (GWA) methods to map quantitative trait loci (QTL) in the simulated dataset provided by the 12(th )QTLMAS workshop in order to derive an effective strategy. RESULTS: A variance component linkage analysis revealed QTLs but with low resolution. Three single-marker based GWA methods were then applied: Transmission Disequilibrium Test and single marker regression, fitting an additive model or a genotype model, on phenotypes pre-corrected for pedigree and fixed effects. These methods detected QTL positions with high concordance to each other and with greater refinement of the linkage signals. Further multiple-marker and haplotype analyses confirmed the results with higher significance. Two-locus interaction analysis detected two epistatic pairs of markers that were not significant by marginal effects. Overall, using stringent Bonferroni thresholds we identified 9 additive QTL and 2 epistatic interactions, which together explained about 12.3% of the corrected phenotypic variance. CONCLUSION: The combination of methods that are robust against population stratification, like QTDT, with flexible linear models that take account of the family structure provided consistent results. Extensive simulations are still required to determine appropriate thresholds for more advanced model including epistasis.
format Text
id pubmed-2654500
institution National Center for Biotechnology Information
language English
publishDate 2009
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-26545002009-03-13 A combined strategy for quantitative trait loci detection by genome-wide association Lam, Alex C Powell, Joseph Wei, Wen-Hua de Koning, Dirk-Jan Haley, Chris S BMC Proc Proceedings BACKGROUND: We applied a range of genome-wide association (GWA) methods to map quantitative trait loci (QTL) in the simulated dataset provided by the 12(th )QTLMAS workshop in order to derive an effective strategy. RESULTS: A variance component linkage analysis revealed QTLs but with low resolution. Three single-marker based GWA methods were then applied: Transmission Disequilibrium Test and single marker regression, fitting an additive model or a genotype model, on phenotypes pre-corrected for pedigree and fixed effects. These methods detected QTL positions with high concordance to each other and with greater refinement of the linkage signals. Further multiple-marker and haplotype analyses confirmed the results with higher significance. Two-locus interaction analysis detected two epistatic pairs of markers that were not significant by marginal effects. Overall, using stringent Bonferroni thresholds we identified 9 additive QTL and 2 epistatic interactions, which together explained about 12.3% of the corrected phenotypic variance. CONCLUSION: The combination of methods that are robust against population stratification, like QTDT, with flexible linear models that take account of the family structure provided consistent results. Extensive simulations are still required to determine appropriate thresholds for more advanced model including epistasis. BioMed Central 2009-02-23 /pmc/articles/PMC2654500/ /pubmed/19278545 Text en Copyright © 2009 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
Powell, Joseph
Wei, Wen-Hua
de Koning, Dirk-Jan
Haley, Chris S
A combined strategy for quantitative trait loci detection by genome-wide association
title A combined strategy for quantitative trait loci detection by genome-wide association
title_full A combined strategy for quantitative trait loci detection by genome-wide association
title_fullStr A combined strategy for quantitative trait loci detection by genome-wide association
title_full_unstemmed A combined strategy for quantitative trait loci detection by genome-wide association
title_short A combined strategy for quantitative trait loci detection by genome-wide association
title_sort combined strategy for quantitative trait loci detection by genome-wide association
topic Proceedings
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654500/
https://www.ncbi.nlm.nih.gov/pubmed/19278545
work_keys_str_mv AT lamalexc acombinedstrategyforquantitativetraitlocidetectionbygenomewideassociation
AT powelljoseph acombinedstrategyforquantitativetraitlocidetectionbygenomewideassociation
AT weiwenhua acombinedstrategyforquantitativetraitlocidetectionbygenomewideassociation
AT dekoningdirkjan acombinedstrategyforquantitativetraitlocidetectionbygenomewideassociation
AT haleychriss acombinedstrategyforquantitativetraitlocidetectionbygenomewideassociation
AT lamalexc combinedstrategyforquantitativetraitlocidetectionbygenomewideassociation
AT powelljoseph combinedstrategyforquantitativetraitlocidetectionbygenomewideassociation
AT weiwenhua combinedstrategyforquantitativetraitlocidetectionbygenomewideassociation
AT dekoningdirkjan combinedstrategyforquantitativetraitlocidetectionbygenomewideassociation
AT haleychriss combinedstrategyforquantitativetraitlocidetectionbygenomewideassociation