Linked Life Data

20639398

Source:http://linkedlifedata.com/resource/pubmed/id/20639398

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2010-9-9
pubmed:abstractText
To pinpoint true positive single-nucleotide polymorphism (SNP) associations in a genome-wide association study (GWAS) of rheumatoid arthritis (RA), we categorize genetic loci by external knowledge. We test both the 'enrichment of associated loci' in a locus category and the 'combined association' of a locus category. The former is quantified by the odds ratio for the presence of SNP associations at the loci of a category, whereas the latter is quantified by the number of loci in a category that have SNP associations. These measures are compared with their expected values as obtained from the permutation of the affection status. To account for linkage disequilibrium (LD) among SNPs, we view each LD block as a genetic locus. Positional candidates were defined as loci implicated by earlier GWAS results, whereas functional candidates were defined by annotations regarding the molecular roles of genes, such as gene ontology categories. As expected, immune-related categories show the largest enrichment signal, although it is not very strong. The intersection of positional and functional candidate information predicts novel RA loci near the genes TEC/TXK, MBL2 and PIK3R1/CD180. Notably, a combined association signal is not only produced by immune-related categories, but also by most other categories and even randomly defined categories. The unspecific quality of these signals limits the possible conclusions from combined association tests. It also reduces the magnitude of enrichment test results. These unspecific signals might result from common variants of small effect and hardly concentrated in candidate categories, or an inflated size of associated regions from weak LD with infrequent mutations.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1460-2083
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3863-72
pubmed:dateRevised
2011-10-3
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Locus category based analysis of a large genome-wide association study of rheumatoid arthritis.
pubmed:affiliation
Robert S. Boas Center for Human Genetics and Genomics, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA. jan.freudenberg@nslij-genetics.org
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural