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Genome-wide Two-marker linkage disequilibrium mapping of quantitative trait loci
BACKGROUND: In a natural population, the alleles of multiple tightly linked loci on the same chromosome co-segregate and are passed non-randomly from generation to generation. Capitalizing on this phenomenon, a group of mapping methods, commonly referred to as the linkage disequilibrium-based mappin...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4015628/ https://www.ncbi.nlm.nih.gov/pubmed/24507412 http://dx.doi.org/10.1186/1471-2156-15-20 |
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author | Yang, Jie Zhu, Wei Chen, Jiansong Zhang, Qiao Wu, Song |
author_facet | Yang, Jie Zhu, Wei Chen, Jiansong Zhang, Qiao Wu, Song |
author_sort | Yang, Jie |
collection | PubMed |
description | BACKGROUND: In a natural population, the alleles of multiple tightly linked loci on the same chromosome co-segregate and are passed non-randomly from generation to generation. Capitalizing on this phenomenon, a group of mapping methods, commonly referred to as the linkage disequilibrium-based mapping (LD mapping), have been developed recently for detecting genetic associations. However, most current LD mapping methods mainly employed single-marker analysis, overlooking the rich information contained within adjacent linked loci. RESULTS: We extend the single-marker LD mapping to include two linked loci and explicitly incorporate their LD information into genetic mapping models (tmLD). We establish the theoretical foundations for the tmLD mapping method and also provide a thorough examination of its statistical properties. Our simulation studies demonstrate that the tmLD mapping method significantly improves the detection power of association compared to the single-marker based and also haplotype based mapping methods. The practical usage and properties of the tmLD mapping method were further elucidated through the analysis of a large-scale dental caries GWAS data set. It shows that the tmLD mapping method can identify significant SNPs that are missed by the traditional single-marker association analysis and haplotype based mapping method. An R package for our proposed method has been developed and is freely available. CONCLUSIONS: The proposed tmLD mapping method is more powerful than single marker mapping generally used in GWAS data analysis. We recommend the usage of this improved method over the traditional single marker association analysis. |
format | Online Article Text |
id | pubmed-4015628 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-40156282014-05-23 Genome-wide Two-marker linkage disequilibrium mapping of quantitative trait loci Yang, Jie Zhu, Wei Chen, Jiansong Zhang, Qiao Wu, Song BMC Genet Methodology Article BACKGROUND: In a natural population, the alleles of multiple tightly linked loci on the same chromosome co-segregate and are passed non-randomly from generation to generation. Capitalizing on this phenomenon, a group of mapping methods, commonly referred to as the linkage disequilibrium-based mapping (LD mapping), have been developed recently for detecting genetic associations. However, most current LD mapping methods mainly employed single-marker analysis, overlooking the rich information contained within adjacent linked loci. RESULTS: We extend the single-marker LD mapping to include two linked loci and explicitly incorporate their LD information into genetic mapping models (tmLD). We establish the theoretical foundations for the tmLD mapping method and also provide a thorough examination of its statistical properties. Our simulation studies demonstrate that the tmLD mapping method significantly improves the detection power of association compared to the single-marker based and also haplotype based mapping methods. The practical usage and properties of the tmLD mapping method were further elucidated through the analysis of a large-scale dental caries GWAS data set. It shows that the tmLD mapping method can identify significant SNPs that are missed by the traditional single-marker association analysis and haplotype based mapping method. An R package for our proposed method has been developed and is freely available. CONCLUSIONS: The proposed tmLD mapping method is more powerful than single marker mapping generally used in GWAS data analysis. We recommend the usage of this improved method over the traditional single marker association analysis. BioMed Central 2014-02-08 /pmc/articles/PMC4015628/ /pubmed/24507412 http://dx.doi.org/10.1186/1471-2156-15-20 Text en Copyright © 2014 Yang 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 credited. |
spellingShingle | Methodology Article Yang, Jie Zhu, Wei Chen, Jiansong Zhang, Qiao Wu, Song Genome-wide Two-marker linkage disequilibrium mapping of quantitative trait loci |
title | Genome-wide Two-marker linkage disequilibrium mapping of quantitative trait loci |
title_full | Genome-wide Two-marker linkage disequilibrium mapping of quantitative trait loci |
title_fullStr | Genome-wide Two-marker linkage disequilibrium mapping of quantitative trait loci |
title_full_unstemmed | Genome-wide Two-marker linkage disequilibrium mapping of quantitative trait loci |
title_short | Genome-wide Two-marker linkage disequilibrium mapping of quantitative trait loci |
title_sort | genome-wide two-marker linkage disequilibrium mapping of quantitative trait loci |
topic | Methodology Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4015628/ https://www.ncbi.nlm.nih.gov/pubmed/24507412 http://dx.doi.org/10.1186/1471-2156-15-20 |
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