@article{09c0cf3b87924a0483117457b4fccf3f,
title = "A gene pathway analysis highlights the role of cellular adhesion molecules in multiple sclerosis susceptibility",
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.",
keywords = "Cell adhesion molecules, Multiple sclerosis, Pathway analysis, Susceptibility",
author = "V. Damotte and L. Guillot-Noel and Patsopoulos, {N. A.} and L. Madireddy and {El Behi}, M. and {De Jager}, {P. L.} and Baranzini, {S. E.} and I. Cournu-Rebeix and B. Fontaine",
note = "Funding Information: The research leading to these results has received funding from the program {\textquoteleft}Investissements d{\textquoteright}avenir{\textquoteright} ANR-10-IAIHU-06. We thank ICM, CIC Piti{\'e}-Salp{\^e}tri{\`e}re, G{\'e}n{\'e}thon, BRC-REFGENSEP{\textquoteright}s and IMSGC{\textquoteright}s members for their help and support as well as Jorge Oksenberg and Pierre-Antoine Gourraud. VD received a travel grant from the Fondation ARSEP and ICM Carnot Institute. Philip L De Jager is a Harry Weaver Neuroscience Scholar of the National MS Society. SEB is a Harry Weaver Neuroscience fellow from the US National MS Society. This investigation was supported (in part) by a Postdoctoral Fellowship from the National Multiple Sclerosis Society to Nikolaos A Patsopoulos (FG 1938-A-1). Funding Information: This study was supported by the Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale, the Fondation pour la Recherche sur la Scl{\'e}rose En Plaques (ARSEP), the Association Franc¸aise contre les Myopathies, GIS-IBISA and ICM Carnot Institute.",
year = "2014",
month = mar,
doi = "10.1038/gene.2013.70",
language = "English",
volume = "15",
pages = "126--132",
journal = "Genes and Immunity",
issn = "1466-4879",
publisher = "Springer Nature",
number = "2",
}