A gene pathway analysis highlights the role of cellular adhesion molecules in multiple sclerosis susceptibility

V Damotte, L Guillot-noel, N A Patsopoulos, L Madireddy, M El Behi, Maria Ban, Sergio Baranzini, Lisa Barcellos, Gary Beecham, Ashley Beecham, Luisa Bernardinelli, David Booth, Steffan Bos, Dorothea Buck, William Bush, Manuel Comabella, Alastair Compston, Chris Cotsapas, Isabelle Cournu-rebeix, Bruce CreeSandra D'alfonso, Mark Daly, Vincent Damotte, Mary Davis, Paul De Bakker, Philip L De Jager, Benedicte Dubois, Federica Esposito, Bertrand Fontaine, An Goris, Pierre-antoine Gourraud, Todd Green, Elisabeth Gulowsen Celius, Athena Hadjixenofontos, David Hafler, Jonathan Haines, Hanne F Flinstad, Stephen Hauser, Clive Hawkins, Bernhard Hemmer, Jan Hillert, Rogier Hintzen, Dana Horáková, Adrian J Ivinson, Anu Kemppinen, Jun-ichi Kira, Ingrid Kockum, Robin Lincoln, Roland Martin, Filippo Martinelli Boneschi, Jacob L Mccauley, Inger-lise Mero, Jorge Oksenberg, Tomas Olsson, Annette Oturai, Aarno Palotie, Nikolaos Patsopoulos, Margaret Pericak-vance, John Rioux, Janna Saarela, Stephen Sawcer, Nathalie Schnetz-boutaud, Finn Sellebjerg, Helle Soendergaard, Per Soelberg Sorensen, Anne Spurkland, Jim Stankovich, Graeme Stewart, Bruce Taylor, Anna Ticca, Sandra West, Frauke Zipp, Peter Donnelly, Ines Barroso, Jenefer M Blackwell, Elvira Bramon, Matthew A Brown, Juan P Casas, Aiden Corvin, Janusz Jankowski, Hugh S Markus, Christopher G Mathew, Colin N A Palmer, Robert Plomin, Anna Rautanen, Stephen Sawcer, Richard C Trembath, Ananth C Viswanathan, Nicholas W Wood, Chris C A Spencer, Gavin Band, Céline Bellenguez, Colin Freeman, Garrett Hellenthal, Eleni Giannoulatou, Matti Pirinen, Richard Pearson, Amy Strange, Zhan Su, Damjan Vukcevic, Peter Donnelly, Cordelia Langford, Sarah E Hunt, Sarah Edkins, Rhian Gwilliam, Hannah Blackburn, Suzannah J Bumpstead, Serge Dronov, Matthew Gillman, Emma Gray, Naomi Hammond, Alagurevathi Jayakumar, Owen T Mccann, Jennifer Liddle, Simon C Potter, Rathi Ravindrarajah, Michelle Ricketts, Matthew J Waller, Paul Weston, Sara Widaa, Pamela Whittaker, Ines Barroso, Panos Deloukas, Alexander Dilthey, Stephen Leslie, Loukas Moutsianas, Marc L Perez, Gil Mcvean, Christopher G Mathew, Jenefer M Blackwell, Matthew A Brown, Aiden Corvin, Mark I Mccarthy, Chris C A Spencer, P L De Jager, S E Baranzini, I Cournu-rebeix, B Fontaine

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Genome-wide association studies (GWASs) perform per-SNP association tests to identify variants involved in disease or trait susceptibility. However, such an approach is not powerful enough to unravel genes that are not individually contributing to the disease/trait, but that may have a role in interaction with other genes as a group. Pathway analysis is an alternative way to highlight such group of genes. Using SNP association P-values from eight multiple sclerosis (MS) GWAS data sets, we performed a candidate pathway analysis for MS susceptibility by considering genes interacting in the cell adhesion molecule (CAMs) biological pathway using Cytoscape software. This network is a strong candidate, as it is involved in the crossing of the blood–brain barrier by the T cells, an early event in MS pathophysiology, and is used as an efficient therapeutic target. We drew up a list of 76 genes belonging to the CAM network. We highlighted 64 networks enriched with CAM genes with low P-values. Filtering by a percentage of CAM genes up to 50% and rejecting enriched signals mainly driven by transcription factors, we highlighted five networks associated with MS susceptibility. One of them, constituted of ITGAL, ICAM1 and ICAM3 genes, could be of interest to develop novel therapeutic targets.
Original languageEnglish
Article numberN/A
Pages (from-to)126-132
Number of pages7
JournalGENES AND IMMUNITY
Volume15
Issue number2
DOIs
Publication statusPublished - Mar 2014

Keywords

  • Multiple sclerosis
  • Susceptibility
  • Pathway analysis
  • Cell adhesion
  • Molecules

Fingerprint

Dive into the research topics of 'A gene pathway analysis highlights the role of cellular adhesion molecules in multiple sclerosis susceptibility'. Together they form a unique fingerprint.

Cite this