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The complete linkage disequilibrium test: a test that points to causative mutations underlying quantitative traits
BACKGROUND: Genetically, SNP that are in complete linkage disequilibrium with the causative SNP cannot be distinguished from the causative SNP. The Complete Linkage Disequilibrium (CLD) test presented here tests whether a SNP is in complete LD with the causative mutation or not. The performance of t...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3118233/ https://www.ncbi.nlm.nih.gov/pubmed/21605351 http://dx.doi.org/10.1186/1297-9686-43-20 |
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author | Uleberg, Eivind Meuwissen, Theo HE |
author_facet | Uleberg, Eivind Meuwissen, Theo HE |
author_sort | Uleberg, Eivind |
collection | PubMed |
description | BACKGROUND: Genetically, SNP that are in complete linkage disequilibrium with the causative SNP cannot be distinguished from the causative SNP. The Complete Linkage Disequilibrium (CLD) test presented here tests whether a SNP is in complete LD with the causative mutation or not. The performance of the CLD test is evaluated in 1000 simulated datasets. METHODS: The CLD test consists of two steps i.e. analysis I and analysis II. Analysis I consists of an association analysis of the investigated region. The log-likelihood values from analysis I are next ranked in descending order and in analysis II the CLD test evaluates differences in log-likelihood ratios between the best and second best markers. Under the null-hypothesis distribution, the best SNP is in greater LD with the QTL than the second best, while under the alternative-CLD-hypothesis, the best SNP is alike-in-state with the QTL. To find a significance threshold, the test was also performed on data excluding the causative SNP. The 5(th), 10(th )and 50(th )highest T(CLD )value from 1000 replicated analyses were used to control the type-I-error rate of the test at p = 0.005, p = 0.01 and p = 0.05, respectively. RESULTS: In a situation where the QTL explained 48% of the phenotypic variance analysis I detected a QTL in 994 replicates (p = 0.001), where 972 were positioned in the correct QTL position. When the causative SNP was excluded from the analysis, 714 replicates detected evidence of a QTL (p = 0.001). In analysis II, the CLD test confirmed 280 causative SNP from 1000 simulations (p = 0.05), i.e. power was 28%. When the effect of the QTL was reduced by doubling the error variance, the power of the test reduced relatively little to 23%. When sequence data were used, the power of the test reduced to 16%. All SNP that were confirmed by the CLD test were positioned in the correct QTL position. CONCLUSIONS: The CLD test can provide evidence for a causative SNP, but its power may be low in situations with closely linked markers. In such situations, also functional evidence will be needed to definitely conclude whether the SNP is causative or not. |
format | Online Article Text |
id | pubmed-3118233 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-31182332011-06-19 The complete linkage disequilibrium test: a test that points to causative mutations underlying quantitative traits Uleberg, Eivind Meuwissen, Theo HE Genet Sel Evol Research BACKGROUND: Genetically, SNP that are in complete linkage disequilibrium with the causative SNP cannot be distinguished from the causative SNP. The Complete Linkage Disequilibrium (CLD) test presented here tests whether a SNP is in complete LD with the causative mutation or not. The performance of the CLD test is evaluated in 1000 simulated datasets. METHODS: The CLD test consists of two steps i.e. analysis I and analysis II. Analysis I consists of an association analysis of the investigated region. The log-likelihood values from analysis I are next ranked in descending order and in analysis II the CLD test evaluates differences in log-likelihood ratios between the best and second best markers. Under the null-hypothesis distribution, the best SNP is in greater LD with the QTL than the second best, while under the alternative-CLD-hypothesis, the best SNP is alike-in-state with the QTL. To find a significance threshold, the test was also performed on data excluding the causative SNP. The 5(th), 10(th )and 50(th )highest T(CLD )value from 1000 replicated analyses were used to control the type-I-error rate of the test at p = 0.005, p = 0.01 and p = 0.05, respectively. RESULTS: In a situation where the QTL explained 48% of the phenotypic variance analysis I detected a QTL in 994 replicates (p = 0.001), where 972 were positioned in the correct QTL position. When the causative SNP was excluded from the analysis, 714 replicates detected evidence of a QTL (p = 0.001). In analysis II, the CLD test confirmed 280 causative SNP from 1000 simulations (p = 0.05), i.e. power was 28%. When the effect of the QTL was reduced by doubling the error variance, the power of the test reduced relatively little to 23%. When sequence data were used, the power of the test reduced to 16%. All SNP that were confirmed by the CLD test were positioned in the correct QTL position. CONCLUSIONS: The CLD test can provide evidence for a causative SNP, but its power may be low in situations with closely linked markers. In such situations, also functional evidence will be needed to definitely conclude whether the SNP is causative or not. BioMed Central 2011-05-23 /pmc/articles/PMC3118233/ /pubmed/21605351 http://dx.doi.org/10.1186/1297-9686-43-20 Text en Copyright ©2011 Uleberg and Meuwissen; 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 | Research Uleberg, Eivind Meuwissen, Theo HE The complete linkage disequilibrium test: a test that points to causative mutations underlying quantitative traits |
title | The complete linkage disequilibrium test: a test that points to causative mutations underlying quantitative traits |
title_full | The complete linkage disequilibrium test: a test that points to causative mutations underlying quantitative traits |
title_fullStr | The complete linkage disequilibrium test: a test that points to causative mutations underlying quantitative traits |
title_full_unstemmed | The complete linkage disequilibrium test: a test that points to causative mutations underlying quantitative traits |
title_short | The complete linkage disequilibrium test: a test that points to causative mutations underlying quantitative traits |
title_sort | complete linkage disequilibrium test: a test that points to causative mutations underlying quantitative traits |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3118233/ https://www.ncbi.nlm.nih.gov/pubmed/21605351 http://dx.doi.org/10.1186/1297-9686-43-20 |
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