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Integration of association statistics over genomic regions using Bayesian adaptive regression splines

In the search for genetic determinants of complex disease, two approaches to association analysis are most often employed, testing single loci or testing a small group of loci jointly via haplotypes for their relationship to disease status. It is still debatable which of these approaches is more fav...

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Autores principales: Zhang, Xiaohua, Roeder, Kathryn, Wallstrom, Garrick, Devlin, Bernie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3525002/
https://www.ncbi.nlm.nih.gov/pubmed/15601530
http://dx.doi.org/10.1186/1479-7364-1-1-20
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author Zhang, Xiaohua
Roeder, Kathryn
Wallstrom, Garrick
Devlin, Bernie
author_facet Zhang, Xiaohua
Roeder, Kathryn
Wallstrom, Garrick
Devlin, Bernie
author_sort Zhang, Xiaohua
collection PubMed
description In the search for genetic determinants of complex disease, two approaches to association analysis are most often employed, testing single loci or testing a small group of loci jointly via haplotypes for their relationship to disease status. It is still debatable which of these approaches is more favourable, and under what conditions. The former has the advantage of simplicity but suffers severely when alleles at the tested loci are not in linkage disequilibrium (LD) with liability alleles; the latter should capture more of the signal encoded in LD, but is far from simple. The complexity of haplotype analysis could be especially troublesome for association scans over large genomic regions, which, in fact, is becoming the standard design. For these reasons, the authors have been evaluating statistical methods that bridge the gap between single-locus and haplotype-based tests. In this article, they present one such method, which uses non-parametric regression techniques embodied by Bayesian adaptive regression splines (BARS). For a set of markers falling within a common genomic region and a corresponding set of single-locus association statistics, the BARS procedure integrates these results into a single test by examining the class of smooth curves consistent with the data. The non-parametric BARS procedure generally finds no signal when no liability allele exists in the tested region (ie it achieves the specified size of the test) and it is sensitive enough to pick up signals when a liability allele is present. The BARS procedure provides a robust and potentially powerful alternative to classical tests of association, diminishes the multiple testing problem inherent in those tests and can be applied to a wide range of data types, including genotype frequencies estimated from pooled samples.
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spelling pubmed-35250022013-01-10 Integration of association statistics over genomic regions using Bayesian adaptive regression splines Zhang, Xiaohua Roeder, Kathryn Wallstrom, Garrick Devlin, Bernie Hum Genomics Primary Research In the search for genetic determinants of complex disease, two approaches to association analysis are most often employed, testing single loci or testing a small group of loci jointly via haplotypes for their relationship to disease status. It is still debatable which of these approaches is more favourable, and under what conditions. The former has the advantage of simplicity but suffers severely when alleles at the tested loci are not in linkage disequilibrium (LD) with liability alleles; the latter should capture more of the signal encoded in LD, but is far from simple. The complexity of haplotype analysis could be especially troublesome for association scans over large genomic regions, which, in fact, is becoming the standard design. For these reasons, the authors have been evaluating statistical methods that bridge the gap between single-locus and haplotype-based tests. In this article, they present one such method, which uses non-parametric regression techniques embodied by Bayesian adaptive regression splines (BARS). For a set of markers falling within a common genomic region and a corresponding set of single-locus association statistics, the BARS procedure integrates these results into a single test by examining the class of smooth curves consistent with the data. The non-parametric BARS procedure generally finds no signal when no liability allele exists in the tested region (ie it achieves the specified size of the test) and it is sensitive enough to pick up signals when a liability allele is present. The BARS procedure provides a robust and potentially powerful alternative to classical tests of association, diminishes the multiple testing problem inherent in those tests and can be applied to a wide range of data types, including genotype frequencies estimated from pooled samples. BioMed Central 2003-11-01 /pmc/articles/PMC3525002/ /pubmed/15601530 http://dx.doi.org/10.1186/1479-7364-1-1-20 Text en Copyright ©2003 Henry Stewart Publications
spellingShingle Primary Research
Zhang, Xiaohua
Roeder, Kathryn
Wallstrom, Garrick
Devlin, Bernie
Integration of association statistics over genomic regions using Bayesian adaptive regression splines
title Integration of association statistics over genomic regions using Bayesian adaptive regression splines
title_full Integration of association statistics over genomic regions using Bayesian adaptive regression splines
title_fullStr Integration of association statistics over genomic regions using Bayesian adaptive regression splines
title_full_unstemmed Integration of association statistics over genomic regions using Bayesian adaptive regression splines
title_short Integration of association statistics over genomic regions using Bayesian adaptive regression splines
title_sort integration of association statistics over genomic regions using bayesian adaptive regression splines
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3525002/
https://www.ncbi.nlm.nih.gov/pubmed/15601530
http://dx.doi.org/10.1186/1479-7364-1-1-20
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