Linked Life Data

15185403

Source:http://linkedlifedata.com/resource/pubmed/id/15185403

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-6-8
pubmed:abstractText
Etiologic heterogeneity is a fundamental feature of complex disease etiology; genetic linkage analysis methods to map genes for complex traits that acknowledge the presence of genetic heterogeneity are likely to have greater power to identify subtle changes in complex biologic systems. We investigate the use of trait-related covariates to examine evidence for linkage in the presence of heterogeneity. Ordered-subset analysis (OSA) identifies subsets of families defined by the level of a trait-related covariate that provide maximal evidence for linkage, without requiring a priori specification of the subset. We propose that examining evidence for linkage in the subset directly may result in a more etiologically homogeneous sample. In turn, the reduced impact of heterogeneity will result in increased overall evidence for linkage to a specific region and a more distinct lod score peak. In addition, identification of a subset defined by a specific trait-related covariate showing increased evidence for linkage may help refine the list of candidate genes in a given region and suggest a useful sample in which to begin searching for trait-associated polymorphisms. This method provides a means to begin to bridge the gap between initial identification of linkage and identification of the disease predisposing variant(s) within a region when mapping genes for complex diseases. We illustrate this method by analyzing data on breast cancer age of onset and chromosome 17q [Hall et al., 1990, Science 250:1684-1689]. We evaluate OSA using simulation studies under a variety of genetic models.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0741-0395
pubmed:author
pubmed:copyrightInfo
Copyright 2004 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
53-63
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Ordered subset analysis in genetic linkage mapping of complex traits.
pubmed:affiliation
Section of Medical Genetics, Department of Medicine, Center for Human Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA. Elizabeth.Hauser@duke.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't