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

2014; Springer Nature; Volume: 15; Issue: 2 Linguagem: Inglês

10.1038/gene.2013.70

1476-5470

Vincent Damotte, Léna Guillot‐Noël, Nikolaos A. Patsopoulos, Lohith Madireddy, Mohamed El Behi, Maria Ban, Sergio E. Baranzini, Lisa F. Barcellos, Gary W. Beecham, Ashley Beecham, Luisa Bernardinelli, David J. Booth, Steffan D. Bos, Dorothea Buck, William S. Bush, Manuel Comabella, Alastair Compston, Chris Cotsapas, Isabelle Cournu‐Rebeix, Bruce Cree, Sandra D’Alfonso, Mark J. Daly, Vincent Damotte, Mary F. Davis, Paul I. W. de Bakker, Philip L. De Jager, Bénédicte Dubois, Federica Esposito, Bertrand Fontaine, An Goris, Pierre‐Antoine Gourraud, Todd J. Green, Elisabeth Gulowsen Celius, Athena Hadjixenofontos, David A. Hafler, Jonathan L. Haines, Hanne F Flinstad, Stephen L. Hauser, Clive Hawkins, Bernhard Hemmer, Jan Hillert, Rogier Hintzen, Dana Horáková, Adrian J. Ivinson, Anu Kemppinen, Jun‐ichi Kira, Ingrid Kockum, Robin Lincoln, Roland Martinꝉ, Filippo Martinelli Boneschi, Jacob L. McCauley, Inger‐Lise Mero, Jorge R. Oksenberg, Tomas Olsson, Annette Oturai, Aarno Palotie, Nikolaos A. Patsopoulos, Margaret A Pericak‐Vance, John D. Rioux, Janna Saarela, Stephen Sawcer, Nathalie Schnetz‐Boutaud, Finn Sellebjerg, Helle Bach Soendergaard, Per Soelberg Sørensen, Anne Spurkland, Jim Stankovich, Graeme J. Stewart, Bruce Taylor, Anna Ticca, Sandra G. West, Frauke Zipp, Peter Donnelly, Inês Barroso, Jenefer M. Blackwell, Elvira Bramon, Matthew A. Brown, Juan P. Casas, Aiden Corvin, Janusz Jankowski, Hugh S. Markus, Christopher G. Mathew, Nicholette D. Palmer, Robert Plomin, Anna Rautanen, Stephen Sawcer, Richard C. Trembath, Ananth C. Viswanathan, Nicholas Wood, Chris C. A. Spencer, Gavin Band, Céline Bellenguez, Colin Freeman, Garrett Hellenthal, Eleni Giannoulatou, Matti Pirinen, Richard D. Pearson, Amy Strange, Zhan Su, Damjan Vukcevic, Peter Donnelly, Cordelia Langford, Sarah 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 Potter, Rathi Ravindrarajah, Michelle Ricketts, Matthew Waller, Paul A. Weston, Sara Widaa, Pamela Whittaker, Inês Barroso, Panos Deloukas, Alexander Dilthey, Stephen Leslie, Loukas Moutsianas, M. L. Perez, Gil McVean, Christopher G. Mathew, Jenefer M. Blackwell, Matthew A. Brown, Aiden Corvin, Mark I. McCarthy, Chris C. A. Spencer, Philip L. De Jager, Sergio E. Baranzini, Isabelle Cournu‐Rebeix, Bertrand Fontaine,

RNA regulation and disease

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.