Imperial College London

Professor Paul M. Matthews

Faculty of MedicineDepartment of Medicine

Edmond and Lily Safra Chair and Head of Brain Sciences
 
 
 
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Contact

 

+44 (0)20 7594 2855p.matthews

 
 
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Assistant

 

Ms Siobhan Dillon +44 (0)20 7594 2855

 
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Location

 

E502Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Baranzini:2009:hmg/ddp120,
author = {Baranzini, SE and Galwey, NW and Wang, J and Khankhanian, P and Lindberg, R and Pelletier, D and Wu, W and Uitdehaag, BMJ and Kappos, L and Polman, CH and Matthews, PM and Hauser, SL and Gibson, RA and Oksenberg, JR and Barnes, MR},
doi = {hmg/ddp120},
journal = {HUMAN MOLECULAR GENETICS},
pages = {2078--2090},
title = {Pathway and network-based analysis of genome-wide association studies in multiple sclerosis},
url = {http://dx.doi.org/10.1093/hmg/ddp120},
volume = {18},
year = {2009}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Genome-wide association studies (GWAS) testing several hundred thousand SNPs have been performed inmultiple sclerosis (MS) and other complex diseases. Typically, the number of markers in which the evidencefor association exceeds the genome-wide significance threshold is very small, and markers that do notexceed this threshold are generally neglected. Classical statistical analysis of these datasets in MS revealedgenes with known immunological functions. However, many of the markers showing modest associationmay represent false negatives. We hypothesize that certain combinations of genes flagged by these markerscan be identified if they belong to a common biological pathway. Here we conduct a pathway-oriented analysisof two GWAS in MS that takes into account all SNPs with nominal evidence of association (P<0.05). Gene-wiseP-values were superimposed on a human protein interaction network and searches were conducted to identifysub-networks containing a higher proportion of genes associated with MS than expected by chance. Thesesub-networks, and others generated at random as a control, were categorized for membership of biologicalpathways. GWAS from eight other diseases were analyzed to assess the specificity of the pathways identified.In the MS datasets, we identified sub-networks of genes from several immunological pathways including celladhesion, communication and signaling. Remarkably, neural pathways, namely axon-guidance and synapticpotentiation, were also over-represented in MS. In addition to the immunological pathways previously ident-ified, we report here for the first time the potential involvement of neural pathways in MS susceptibility.
AU - Baranzini,SE
AU - Galwey,NW
AU - Wang,J
AU - Khankhanian,P
AU - Lindberg,R
AU - Pelletier,D
AU - Wu,W
AU - Uitdehaag,BMJ
AU - Kappos,L
AU - Polman,CH
AU - Matthews,PM
AU - Hauser,SL
AU - Gibson,RA
AU - Oksenberg,JR
AU - Barnes,MR
DO - hmg/ddp120
EP - 2090
PY - 2009///
SN - 0964-6906
SP - 2078
TI - Pathway and network-based analysis of genome-wide association studies in multiple sclerosis
T2 - HUMAN MOLECULAR GENETICS
UR - http://dx.doi.org/10.1093/hmg/ddp120
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000265951600017&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - http://hdl.handle.net/10044/1/57619
VL - 18
ER -