Source:http://linkedlifedata.com/resource/pubmed/id/20699326
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
21
|
| pubmed:dateCreated |
2010-10-11
|
| pubmed:abstractText |
The primary genetic risk factor in multiple sclerosis (MS) is the HLA-DRB1*1501 allele; however, much of the remaining genetic contribution to MS has yet to be elucidated. Several lines of evidence support a role for neuroendocrine system involvement in autoimmunity which may, in part, be genetically determined. Here, we comprehensively investigated variation within eight candidate hypothalamic-pituitary-adrenal (HPA) axis genes and susceptibility to MS. A total of 326 SNPs were investigated in a discovery dataset of 1343 MS cases and 1379 healthy controls of European ancestry using a multi-analytical strategy. Random Forests, a supervised machine-learning algorithm, identified eight intronic SNPs within the corticotrophin-releasing hormone receptor 1 or CRHR1 locus on 17q21.31 as important predictors of MS. On the basis of univariate analyses, six CRHR1 variants were associated with decreased risk for disease following a conservative correction for multiple tests. Independent replication was observed for CRHR1 in a large meta-analysis comprising 2624 MS cases and 7220 healthy controls of European ancestry. Results from a combined meta-analysis of all 3967 MS cases and 8599 controls provide strong evidence for the involvement of CRHR1 in MS. The strongest association was observed for rs242936 (OR = 0.82, 95% CI = 0.74-0.90, P = 9.7 × 10(-5)). Replicated CRHR1 variants appear to exist on a single associated haplotype. Further investigation of mechanisms involved in HPA axis regulation and response to stress in MS pathogenesis is warranted.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Nov
|
| pubmed:issn |
1460-2083
|
| pubmed:author |
pubmed-author:BarcellosLisa FLF,
pubmed-author:BartlettSelena ESE,
pubmed-author:BriggsFarren B SFB,
pubmed-author:CompstonAlastairA,
pubmed-author:De JagerPhilip LPL,
pubmed-author:GoldsteinBenjamin ABA,
pubmed-author:HaflerDavid ADA,
pubmed-author:HainesJonathan LJL,
pubmed-author:HauserStephen LSL,
pubmed-author:International Multiple Sclerosis Genetics Consortium,
pubmed-author:IvinsonAdrian JAJ,
pubmed-author:McCauleyJacob LJL,
pubmed-author:OksenbergJorge RJR,
pubmed-author:Pericak-VanceMargaret AMA,
pubmed-author:RiouxJohn DJD,
pubmed-author:SawcerStephen JSJ,
pubmed-author:WangJoanneJ,
pubmed-author:ZuvichRebecca LRL
|
| pubmed:issnType |
Electronic
|
| pubmed:day |
1
|
| pubmed:volume |
19
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
4286-95
|
| pubmed:dateRevised |
2011-11-1
|
| pubmed:meshHeading |
pubmed-meshheading:20699326-Case-Control Studies,
pubmed-meshheading:20699326-Humans,
pubmed-meshheading:20699326-Mass Spectrometry,
pubmed-meshheading:20699326-Multiple Sclerosis,
pubmed-meshheading:20699326-Polymorphism, Single Nucleotide,
pubmed-meshheading:20699326-Receptors, Corticotropin-Releasing Hormone
|
| pubmed:year |
2010
|
| pubmed:articleTitle |
Evidence for CRHR1 in multiple sclerosis using supervised machine learning and meta-analysis in 12,566 individuals.
|
| pubmed:affiliation |
Genetic Epidemiology and Genomics Laboratory, Division of Epidemiology, School of Public Health, CA 94720-7356, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Meta-Analysis,
Research Support, N.I.H., Extramural
|