Linked Life Data

12215896

Source:http://linkedlifedata.com/resource/pubmed/id/12215896

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2002-9-6
pubmed:abstractText
Systemic lupus erythematosus (SLE) appears to be the consequence of complex genetics and of only partly understood environmental contributions. Previous work by ourselves and by others has established genetic effects on 1q, 2q, 4p, 6p, and 16p using SLE as the phenotype. However, individual SLE affecteds are extraordinarily different from one another by clinical and laboratory measures. This variation may have a genetic basis; if so, it is advantageous to incorporate measures of between-family clinical variability as covariates in a genetic linkage analysis of affected relative pairs (ARPs) to allow for locus heterogeneity. This approach was applied to genome scan marker data from 160 pedigrees multiplex for SLE and containing 202 ARPs. Because the number of potential covariates was large, we used both ad hoc methods and formal principal components analysis to construct four composite covariates using the SLE classification criteria plus age of onset, ethnicity, and sex. Linkage analysis without covariates has detected evidence for linkage at 1q22-24, 2q37, 4p16, 12p12-11, and 17p13. Linkage analysis with these covariates uncovered linkage at 13p11, 17q11-25, and 20q12 and greatly improved evidence for linkage at 1q22-24, 2q37, 12p12-11, and 17p13. Follow-up analysis identified the original variables contributing to locus heterogeneity in each of these locations. In conclusion, allowing for locus heterogeneity through the incorporation of covariates in linkage analysis is a useful way to dissect the genetic contributions to SLE and uncover new genetic effects.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1466-4879
pubmed:author
pubmed:issnType
Print
pubmed:volume
3 Suppl 1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
S5-S12
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
A genome screen of systemic lupus erythematosus using affected-relative-pair linkage analysis with covariates demonstrates genetic heterogeneity.
pubmed:affiliation
Department of Epidemiology and Biostatistics, Rammelkamp Center for Education and Research, MetroHealth Campus, Case Western Reserve University, Cleveland, OH 44109-8410, USA. olson@darwin.cwru.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.