Linked Life Data

19217022

Source:http://linkedlifedata.com/resource/pubmed/id/19217022

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2009-10-22
pubmed:abstractText
We present the "sumLINK" statistic--the sum of multipoint LOD scores for the subset of pedigrees with nominally significant linkage evidence at a given locus--as an alternative to common methods to identify susceptibility loci in the presence of heterogeneity. We also suggest the "sumLOD" statistic (the sum of positive multipoint LOD scores) as a companion to the sumLINK. sumLINK analysis identifies genetic regions of extreme consistency across pedigrees without regard to negative evidence from unlinked or uninformative pedigrees. Significance is determined by an innovative permutation procedure based on genome shuffling that randomizes linkage information across pedigrees. This procedure for generating the empirical null distribution may be useful for other linkage-based statistics as well. Using 500 genome-wide analyses of simulated null data, we show that the genome shuffling procedure results in the correct type 1 error rates for both the sumLINK and sumLOD. The power of the statistics was tested using 100 sets of simulated genome-wide data from the alternative hypothesis from GAW13. Finally, we illustrate the statistics in an analysis of 190 aggressive prostate cancer pedigrees from the International Consortium for Prostate Cancer Genetics, where we identified a new susceptibility locus. We propose that the sumLINK and sumLOD are ideal for collaborative projects and meta-analyses, as they do not require any sharing of identifiable data between contributing institutions. Further, loci identified with the sumLINK have good potential for gene localization via statistical recombinant mapping, as, by definition, several linked pedigrees contribute to each peak.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1098-2272
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
628-36
pubmed:dateRevised
2011-9-22
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
The sumLINK statistic for genetic linkage analysis in the presence of heterogeneity.
pubmed:affiliation
Department of Biomedical Informatics, University of Utah School of Medicine, Salt Lake City, Utah 84108-1266, USA. bryce.christensen@utah.edu
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural