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Clique-Based Clustering of Correlated SNPs in a Gene Can Improve Performance of Gene-Based Multi-Bin Linear Combination Test

Gene-based analysis of multiple single nucleotide polymorphisms (SNPs) in a gene region is an alternative to single SNP analysis. The multi-bin linear combination test (MLC) proposed in previous studies utilizes the correlation among SNPs within a gene to construct a gene-based global test. SNPs are...

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Autores principales: Yoo, Yun Joo, Kim, Sun Ah, Bull, Shelley B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539439/
https://www.ncbi.nlm.nih.gov/pubmed/26346579
http://dx.doi.org/10.1155/2015/852341
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author Yoo, Yun Joo
Kim, Sun Ah
Bull, Shelley B.
author_facet Yoo, Yun Joo
Kim, Sun Ah
Bull, Shelley B.
author_sort Yoo, Yun Joo
collection PubMed
description Gene-based analysis of multiple single nucleotide polymorphisms (SNPs) in a gene region is an alternative to single SNP analysis. The multi-bin linear combination test (MLC) proposed in previous studies utilizes the correlation among SNPs within a gene to construct a gene-based global test. SNPs are partitioned into clusters of highly correlated SNPs, and the MLC test statistic quadratically combines linear combination statistics constructed for each cluster. The test has degrees of freedom equal to the number of clusters and can be more powerful than a fully quadratic or fully linear test statistic. In this study, we develop a new SNP clustering algorithm designed to find cliques, which are complete subnetworks of SNPs with all pairwise correlations above a threshold. We evaluate the performance of the MLC test using the clique-based CLQ algorithm versus using the tag-SNP-based LDSelect algorithm. In our numerical power calculations we observed that the two clustering algorithms produce identical clusters about 40~60% of the time, yielding similar power on average. However, because the CLQ algorithm tends to produce smaller clusters with stronger positive correlation, the MLC test is less likely to be affected by the occurrence of opposing signs in the individual SNP effect coefficients.
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spelling pubmed-45394392015-09-06 Clique-Based Clustering of Correlated SNPs in a Gene Can Improve Performance of Gene-Based Multi-Bin Linear Combination Test Yoo, Yun Joo Kim, Sun Ah Bull, Shelley B. Biomed Res Int Research Article Gene-based analysis of multiple single nucleotide polymorphisms (SNPs) in a gene region is an alternative to single SNP analysis. The multi-bin linear combination test (MLC) proposed in previous studies utilizes the correlation among SNPs within a gene to construct a gene-based global test. SNPs are partitioned into clusters of highly correlated SNPs, and the MLC test statistic quadratically combines linear combination statistics constructed for each cluster. The test has degrees of freedom equal to the number of clusters and can be more powerful than a fully quadratic or fully linear test statistic. In this study, we develop a new SNP clustering algorithm designed to find cliques, which are complete subnetworks of SNPs with all pairwise correlations above a threshold. We evaluate the performance of the MLC test using the clique-based CLQ algorithm versus using the tag-SNP-based LDSelect algorithm. In our numerical power calculations we observed that the two clustering algorithms produce identical clusters about 40~60% of the time, yielding similar power on average. However, because the CLQ algorithm tends to produce smaller clusters with stronger positive correlation, the MLC test is less likely to be affected by the occurrence of opposing signs in the individual SNP effect coefficients. Hindawi Publishing Corporation 2015 2015-08-04 /pmc/articles/PMC4539439/ /pubmed/26346579 http://dx.doi.org/10.1155/2015/852341 Text en Copyright © 2015 Yun Joo Yoo et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Yoo, Yun Joo
Kim, Sun Ah
Bull, Shelley B.
Clique-Based Clustering of Correlated SNPs in a Gene Can Improve Performance of Gene-Based Multi-Bin Linear Combination Test
title Clique-Based Clustering of Correlated SNPs in a Gene Can Improve Performance of Gene-Based Multi-Bin Linear Combination Test
title_full Clique-Based Clustering of Correlated SNPs in a Gene Can Improve Performance of Gene-Based Multi-Bin Linear Combination Test
title_fullStr Clique-Based Clustering of Correlated SNPs in a Gene Can Improve Performance of Gene-Based Multi-Bin Linear Combination Test
title_full_unstemmed Clique-Based Clustering of Correlated SNPs in a Gene Can Improve Performance of Gene-Based Multi-Bin Linear Combination Test
title_short Clique-Based Clustering of Correlated SNPs in a Gene Can Improve Performance of Gene-Based Multi-Bin Linear Combination Test
title_sort clique-based clustering of correlated snps in a gene can improve performance of gene-based multi-bin linear combination test
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539439/
https://www.ncbi.nlm.nih.gov/pubmed/26346579
http://dx.doi.org/10.1155/2015/852341
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