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Genes Immun. 2014 Mar;15(2):126-32. doi: 10.1038/gene.2013.70. Epub 2014 Jan 16.

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

Collaborators (129)

Ban M, Baranzini S, Barcellos L, Beecham G, Beecham A, Bernardinelli L, Booth D, Bos S, Buck D, Bush W, Comabella M, Compston A, Cotsapas C, Cournu-Rebeix I, Cree B, D'Alfonso S, Daly M, Damotte V, Davis M, de Bakker P, De Jager PL, Dubois B, Esposito F, Fontaine B, Goris A, Gourraud PA, Green T, Gulowsen Celius E, Hadjixenofontos A, Hafler D, Haines J, Harbo HF, Hauser S, Hawkins C, Hemmer B, Hillert J, Hintzen R, Horáková D, Ivinson AJ, Kemppinen A, Kira J, Kockum I, Lincoln R, Martin R, Martinelli Boneschi F, McCauley JL, Mero IL, Oksenberg J, Olsson T, Oturai A, Palotie A, Patsopoulos N, Pericak-Vance M, Rioux J, Saarela J, Sawcer S, Schnetz-Boutaud N, Sellebjerg F, Soendergaard H, Soelberg Sorensen P, Spurkland A, Stankovich J, Stewart G, Taylor B, Ticca A, West S, Zipp F, Donnelly P, Barroso I, Blackwell JM, Bramon E, Brown MA, Casas JP, Corvin A, Jankowski J, Markus HS, Mathew CG, Palmer CN, Plomin R, Rautanen A, Sawcer S, Trembath RC, Viswanathan AC, Wood NW, Spencer CC, Band G, Bellenguez C, Freeman C, Hellenthal G, Giannoulatou E, Pirinen M, Pearson R, Strange A, Su Z, Vukcevic D, Donnelly P, Langford C, Hunt SE, Edkins S, Gwilliam R, Blackburn H, Bumpstead SJ, Dronov S, Gillman M, Gray E, Hammond N, Jayakumar A, McCann OT, Liddle J, Potter SC, Ravindrarajah R, Ricketts M, Waller MJ, Weston P, Widaa S, Whittaker P, Barroso I, Deloukas P, Dilthey A, Leslie S, Moutsianas L, Perez ML, McVean G, Mathew CG, Blackwell JM, Brown MA, Corvin A, McCarthy MI, Spencer CC.

Author information

1
UPMC-INSERM-UMR_S 1127-CNRS UMR7225, Paris, France.
2
1] Departments of Neurology and Psychiatry, Institute for the Neurosciences, Brigham & Women's Hospital, Boston, MA, USA [2] Division of Genetics, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA [3] Harvard Medical School, Boston, MA, USA [4] Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
3
Department of Neurology, University of California at San Francisco, Sandler Neurosciences Center, San Francisco, CA, USA.
4
1] UPMC-INSERM-UMR_S 1127-CNRS UMR7225, Paris, France [2] Institut du Cerveau et de la Moelle épinière-ICM, Paris, France.
5
1] Departments of Neurology and Psychiatry, Institute for the Neurosciences, Brigham & Women's Hospital, Boston, MA, USA [2] Harvard Medical School, Boston, MA, USA [3] Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
6
1] UPMC-INSERM-UMR_S 1127-CNRS UMR7225, Paris, France [2] Assistance Publique-Hôpitaux de Paris (AP-HP), Département des Maladies du Systéme Nerveux, Hôpital Pitié-Salpêtrière, Paris, France.

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.

PMID:
24430173
DOI:
10.1038/gene.2013.70
[Indexed for MEDLINE]
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