Bayesian linkage analysis of categorical traits for arbitrary pedigree designs.

Pedigree studies of complex heritable diseases often feature nominal or ordinal phenotypic measurements and missing genetic marker or phenotype data.We have developed a Bayesian method for Linkage analysis of Ordinal and Categorical traits (LOCate) that can analyze complex genealogical structure for...

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Main Authors: Abra Brisbin, Myrna M Weissman, Abby J Fyer, Steven P Hamilton, James A Knowles, Carlos D Bustamante, Jason G Mezey
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2010-08-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC2928726?pdf=render
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author Abra Brisbin
Myrna M Weissman
Abby J Fyer
Steven P Hamilton
James A Knowles
Carlos D Bustamante
Jason G Mezey
author_facet Abra Brisbin
Myrna M Weissman
Abby J Fyer
Steven P Hamilton
James A Knowles
Carlos D Bustamante
Jason G Mezey
author_sort Abra Brisbin
collection DOAJ
description Pedigree studies of complex heritable diseases often feature nominal or ordinal phenotypic measurements and missing genetic marker or phenotype data.We have developed a Bayesian method for Linkage analysis of Ordinal and Categorical traits (LOCate) that can analyze complex genealogical structure for family groups and incorporate missing data. LOCate uses a Gibbs sampling approach to assess linkage, incorporating a simulated tempering algorithm for fast mixing. While our treatment is Bayesian, we develop a LOD (log of odds) score estimator for assessing linkage from Gibbs sampling that is highly accurate for simulated data. LOCate is applicable to linkage analysis for ordinal or nominal traits, a versatility which we demonstrate by analyzing simulated data with a nominal trait, on which LOCate outperforms LOT, an existing method which is designed for ordinal traits. We additionally demonstrate our method's versatility by analyzing a candidate locus (D2S1788) for panic disorder in humans, in a dataset with a large amount of missing data, which LOT was unable to handle.LOCate's accuracy and applicability to both ordinal and nominal traits will prove useful to researchers interested in mapping loci for categorical traits.
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spelling doaj.art-4190a0da4cde46afa2a1259d4ca017e12022-12-21T18:57:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-08-0158e1230710.1371/journal.pone.0012307Bayesian linkage analysis of categorical traits for arbitrary pedigree designs.Abra BrisbinMyrna M WeissmanAbby J FyerSteven P HamiltonJames A KnowlesCarlos D BustamanteJason G MezeyPedigree studies of complex heritable diseases often feature nominal or ordinal phenotypic measurements and missing genetic marker or phenotype data.We have developed a Bayesian method for Linkage analysis of Ordinal and Categorical traits (LOCate) that can analyze complex genealogical structure for family groups and incorporate missing data. LOCate uses a Gibbs sampling approach to assess linkage, incorporating a simulated tempering algorithm for fast mixing. While our treatment is Bayesian, we develop a LOD (log of odds) score estimator for assessing linkage from Gibbs sampling that is highly accurate for simulated data. LOCate is applicable to linkage analysis for ordinal or nominal traits, a versatility which we demonstrate by analyzing simulated data with a nominal trait, on which LOCate outperforms LOT, an existing method which is designed for ordinal traits. We additionally demonstrate our method's versatility by analyzing a candidate locus (D2S1788) for panic disorder in humans, in a dataset with a large amount of missing data, which LOT was unable to handle.LOCate's accuracy and applicability to both ordinal and nominal traits will prove useful to researchers interested in mapping loci for categorical traits.http://europepmc.org/articles/PMC2928726?pdf=render
spellingShingle Abra Brisbin
Myrna M Weissman
Abby J Fyer
Steven P Hamilton
James A Knowles
Carlos D Bustamante
Jason G Mezey
Bayesian linkage analysis of categorical traits for arbitrary pedigree designs.
PLoS ONE
title Bayesian linkage analysis of categorical traits for arbitrary pedigree designs.
title_full Bayesian linkage analysis of categorical traits for arbitrary pedigree designs.
title_fullStr Bayesian linkage analysis of categorical traits for arbitrary pedigree designs.
title_full_unstemmed Bayesian linkage analysis of categorical traits for arbitrary pedigree designs.
title_short Bayesian linkage analysis of categorical traits for arbitrary pedigree designs.
title_sort bayesian linkage analysis of categorical traits for arbitrary pedigree designs
url http://europepmc.org/articles/PMC2928726?pdf=render
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