Ordered‐subset analysis (OSA) for family‐based association mapping of complex traits
Identifieur interne : 000D22 ( Main/Exploration ); précédent : 000D21; suivant : 000D23Ordered‐subset analysis (OSA) for family‐based association mapping of complex traits
Auteurs : Ren-Hua Chung [États-Unis] ; Silke Schmidt [États-Unis] ; Eden R. Martin [États-Unis] ; Elizabeth R. Hauser [États-Unis]Source :
- Genetic Epidemiology [ 0741-0395 ] ; 2008-11.
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Abstract
Association analysis provides a powerful tool for complex disease gene mapping. However, in the presence of genetic heterogeneity, the power for association analysis can be low since only a fraction of the collected families may carry a specific disease susceptibility allele. Ordered‐subset analysis (OSA) is a linkage test that can be powerful in the presence of genetic heterogeneity. OSA uses trait‐related covariates to identify a subset of families that provide the most evidence for linkage. A similar strategy applied to genetic association analysis would likely result in increased power to detect association. Association in the presence of linkage (APL) is a family‐based association test (FBAT) for nuclear families with multiple affected siblings that properly infers missing parental genotypes when linkage is present. We propose here APL‐OSA, which applies the OSA method to the APL statistic to identify a subset of families that provide the most evidence for association. A permutation procedure is used to approximate the distribution of the APL‐OSA statistic under the null hypothesis that there is no relationship between the family‐specific covariate and the family‐specific evidence for allelic association. We performed a comprehensive simulation study to verify that APL‐OSA has the correct type I error rate under the null hypothesis. This simulation study also showed that APL‐OSA can increase power relative to other commonly used association tests (APL, FBAT and FBAT with covariate adjustment) in the presence of genetic heterogeneity. Finally, we applied APL‐OSA to a family study of age‐related macular degeneration, where cigarette smoking was used as a covariate. Genet. Epidemiol. 2008. © 2008 Wiley‐Liss, Inc.
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DOI: 10.1002/gepi.20340
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Hauser</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:3D20476BBA5B3223966E298661D4E9E274FA55FC</idno><date when="2008" year="2008">2008</date><idno type="doi">10.1002/gepi.20340</idno><idno type="url">https://api.istex.fr/document/3D20476BBA5B3223966E298661D4E9E274FA55FC/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">002605</idno><idno type="wicri:Area/Main/Curation">002267</idno><idno type="wicri:Area/Main/Exploration">000D22</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Ordered‐subset analysis (OSA) for family‐based association mapping of complex traits</title><author><name sortKey="Chung, Ren Ua" sort="Chung, Ren Ua" uniqKey="Chung R" first="Ren-Hua" last="Chung">Ren-Hua Chung</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Center for Human Genetics, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Schmidt, Silke" sort="Schmidt, Silke" uniqKey="Schmidt S" first="Silke" last="Schmidt">Silke Schmidt</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Center for Human Genetics, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Martin, Eden R" sort="Martin, Eden R" uniqKey="Martin E" first="Eden R." last="Martin">Eden R. Martin</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Floride</region></placeName><wicri:cityArea>Center for Genetic Epidemiology and Statistical Genetics, Miami Institute for Human Genomics, University of Miami Miller School of Medicine, Miami</wicri:cityArea></affiliation></author><author><name sortKey="Hauser, Elizabeth R" sort="Hauser, Elizabeth R" uniqKey="Hauser E" first="Elizabeth R." last="Hauser">Elizabeth R. Hauser</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Center for Human Genetics, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author></analytic><monogr></monogr><series><title level="j">Genetic Epidemiology</title><title level="j" type="sub">The Official Publication of the International Genetic Epidemiology Society</title><title level="j" type="abbrev">Genet. Epidemiol.</title><idno type="ISSN">0741-0395</idno><idno type="eISSN">1098-2272</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2008-11">2008-11</date><biblScope unit="volume">32</biblScope><biblScope unit="issue">7</biblScope><biblScope unit="page" from="627">627</biblScope><biblScope unit="page" to="637">637</biblScope></imprint><idno type="ISSN">0741-0395</idno></series><idno type="istex">3D20476BBA5B3223966E298661D4E9E274FA55FC</idno><idno type="DOI">10.1002/gepi.20340</idno><idno type="ArticleID">GEPI20340</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0741-0395</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>covariate</term><term>family‐based association analysis</term><term>genetic heterogeneity</term><term>linkage</term><term>ordered‐subset analysis</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Association analysis provides a powerful tool for complex disease gene mapping. However, in the presence of genetic heterogeneity, the power for association analysis can be low since only a fraction of the collected families may carry a specific disease susceptibility allele. Ordered‐subset analysis (OSA) is a linkage test that can be powerful in the presence of genetic heterogeneity. OSA uses trait‐related covariates to identify a subset of families that provide the most evidence for linkage. A similar strategy applied to genetic association analysis would likely result in increased power to detect association. Association in the presence of linkage (APL) is a family‐based association test (FBAT) for nuclear families with multiple affected siblings that properly infers missing parental genotypes when linkage is present. We propose here APL‐OSA, which applies the OSA method to the APL statistic to identify a subset of families that provide the most evidence for association. A permutation procedure is used to approximate the distribution of the APL‐OSA statistic under the null hypothesis that there is no relationship between the family‐specific covariate and the family‐specific evidence for allelic association. We performed a comprehensive simulation study to verify that APL‐OSA has the correct type I error rate under the null hypothesis. This simulation study also showed that APL‐OSA can increase power relative to other commonly used association tests (APL, FBAT and FBAT with covariate adjustment) in the presence of genetic heterogeneity. Finally, we applied APL‐OSA to a family study of age‐related macular degeneration, where cigarette smoking was used as a covariate. Genet. Epidemiol. 2008. © 2008 Wiley‐Liss, Inc.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Caroline du Nord</li><li>Floride</li></region></list><tree><country name="États-Unis"><region name="Caroline du Nord"><name sortKey="Chung, Ren Ua" sort="Chung, Ren Ua" uniqKey="Chung R" first="Ren-Hua" last="Chung">Ren-Hua Chung</name></region><name sortKey="Hauser, Elizabeth R" sort="Hauser, Elizabeth R" uniqKey="Hauser E" first="Elizabeth R." last="Hauser">Elizabeth R. Hauser</name><name sortKey="Martin, Eden R" sort="Martin, Eden R" uniqKey="Martin E" first="Eden R." last="Martin">Eden R. Martin</name><name sortKey="Schmidt, Silke" sort="Schmidt, Silke" uniqKey="Schmidt S" first="Silke" last="Schmidt">Silke Schmidt</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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