Source:http://linkedlifedata.com/resource/pubmed/id/17044847
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
Pt 6
|
pubmed:dateCreated |
2006-10-18
|
pubmed:abstractText |
Characterisation of the interactions between susceptibility loci (epistasis) is central to a full understanding of the genetic aetiology and the molecular pathology of complex diseases. We have examined, in British and French pedigrees, evidence for epistasis between the type 2 diabetes susceptibility loci on chromosomes 1q21-25 and 10q23-26 using two complementary linkage-based approaches. Joint two-locus linkage analysis of 1q and 10q in British pedigrees provided significant evidence for interaction (P < or = 0.003) when comparing a general epistasis model with multiplicative or additive-effects-only models. Conditional linkage analysis (which models epistasis as a deviation from multiplicativity only) confirmed these findings, with significant LOD score increases at the 1q (P = 0.0002) and 10q (P = 0.0023) loci. These analyses provided sizeable reductions in the 1-LOD support intervals for both loci. Analyses of the British and French pedigrees together yielded comparable, but not enhanced, findings, with significant (P < or = 0.003) evidence for epistasis in joint two-locus linkage analysis, and during conditional linkage analysis significant increases in linkage evidence at the 1q (P = 0.0002) and 10q (P = 0.0036) loci. Our findings of epistasis nevertheless substantiate the evidence for genuine genetic effects at both loci, facilitate endeavours to fine-map these loci in population samples, and support further examination of this interaction at the nucleotide level by providing a robust prior hypothesis.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:status |
MEDLINE
|
pubmed:month |
Nov
|
pubmed:issn |
0003-4800
|
pubmed:author |
pubmed-author:BellJ TJT,
pubmed-author:DineGG,
pubmed-author:FarrallMM,
pubmed-author:FraylingT MTM,
pubmed-author:FroguelPP,
pubmed-author:GrovesC JCJ,
pubmed-author:HattersleyA TAT,
pubmed-author:HitmanG AGA,
pubmed-author:McCarthyM IMI,
pubmed-author:VaxillaireMM,
pubmed-author:WalkerMM,
pubmed-author:WiltshireSS
|
pubmed:issnType |
Print
|
pubmed:volume |
70
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
726-37
|
pubmed:dateRevised |
2010-11-18
|
pubmed:meshHeading |
pubmed-meshheading:17044847-Chromosomes, Human, Pair 1,
pubmed-meshheading:17044847-Chromosomes, Human, Pair 10,
pubmed-meshheading:17044847-Diabetes Mellitus, Type 2,
pubmed-meshheading:17044847-Epistasis, Genetic,
pubmed-meshheading:17044847-European Continental Ancestry Group,
pubmed-meshheading:17044847-Genetic Linkage,
pubmed-meshheading:17044847-Genetic Predisposition to Disease,
pubmed-meshheading:17044847-Genetic Variation,
pubmed-meshheading:17044847-Humans,
pubmed-meshheading:17044847-Pedigree
|
pubmed:year |
2006
|
pubmed:articleTitle |
Epistasis between type 2 diabetes susceptibility Loci on chromosomes 1q21-25 and 10q23-26 in northern Europeans.
|
pubmed:affiliation |
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|