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 Cree; Sandra 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

doi:10.1038/gene.2013.70

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 journal › Article › peer-review

27 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 language	English
Article number	N/A
Pages (from-to)	126-132
Number of pages	7
Journal	GENES AND IMMUNITY
Volume	15
Issue number	2
DOIs	https://doi.org/10.1038/gene.2013.70
Publication status	Published - Mar 2014

Keywords

Multiple sclerosis
Susceptibility
Pathway analysis
Cell adhesion
Molecules

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10.1038/gene.2013.70

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Damotte, V., Guillot-noel, L., Patsopoulos, N. A., Madireddy, L., El Behi, M., 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., ... Fontaine, B. (2014). A gene pathway analysis highlights the role of cellular adhesion molecules in multiple sclerosis susceptibility. GENES AND IMMUNITY, 15(2), 126-132. Article N/A. https://doi.org/10.1038/gene.2013.70

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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 = "Multiple sclerosis, Susceptibility, Pathway analysis, Cell adhesion, Molecules",

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

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 [academic journals on nature.com]",

number = "2",

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Damotte, V, Guillot-noel, L, Patsopoulos, NA, Madireddy, L, El Behi, M, 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, P, Green, T, Gulowsen Celius, E, Hadjixenofontos, A, Hafler, D, Haines, J, Flinstad, 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, I, 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, CNA, Plomin, R, Rautanen, A, Sawcer, S, Trembath, RC , Viswanathan, AC, Wood, NW, Spencer, CCA, 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, CCA, De Jager, PL, Baranzini, SE, Cournu-rebeix, I & Fontaine, B 2014, 'A gene pathway analysis highlights the role of cellular adhesion molecules in multiple sclerosis susceptibility', GENES AND IMMUNITY, vol. 15, no. 2, N/A, pp. 126-132. https://doi.org/10.1038/gene.2013.70

TY - JOUR

T1 - A gene pathway analysis highlights the role of cellular adhesion molecules in multiple sclerosis susceptibility

AU - Damotte, V

AU - Guillot-noel, L

AU - Patsopoulos, N A

AU - Madireddy, L

AU - El Behi, M

AU - Ban, Maria

AU - Baranzini, Sergio

AU - Barcellos, Lisa

AU - Beecham, Gary

AU - Beecham, Ashley

AU - Bernardinelli, Luisa

AU - Booth, David

AU - Bos, Steffan

AU - Buck, Dorothea

AU - Bush, William

AU - Comabella, Manuel

AU - Compston, Alastair

AU - Cotsapas, Chris

AU - Cournu-rebeix, Isabelle

AU - Cree, Bruce

AU - D'alfonso, Sandra

AU - Daly, Mark

AU - Damotte, Vincent

AU - Davis, Mary

AU - De Bakker, Paul

AU - De Jager, Philip L

AU - Dubois, Benedicte

AU - Esposito, Federica

AU - Fontaine, Bertrand

AU - Goris, An

AU - Gourraud, Pierre-antoine

AU - Green, Todd

AU - Gulowsen Celius, Elisabeth

AU - Hadjixenofontos, Athena

AU - Hafler, David

AU - Haines, Jonathan

AU - Flinstad, Hanne F

AU - Hauser, Stephen

AU - Hawkins, Clive

AU - Hemmer, Bernhard

AU - Hillert, Jan

AU - Hintzen, Rogier

AU - Horáková, Dana

AU - Ivinson, Adrian J

AU - Kemppinen, Anu

AU - Kira, Jun-ichi

AU - Kockum, Ingrid

AU - Lincoln, Robin

AU - Martin, Roland

AU - Martinelli Boneschi, Filippo

AU - Mccauley, Jacob L

AU - Mero, Inger-lise

AU - Oksenberg, Jorge

AU - Olsson, Tomas

AU - Oturai, Annette

AU - Palotie, Aarno

AU - Patsopoulos, Nikolaos

AU - Pericak-vance, Margaret

AU - Rioux, John

AU - Saarela, Janna

AU - Sawcer, Stephen

AU - Schnetz-boutaud, Nathalie

AU - Sellebjerg, Finn

AU - Soendergaard, Helle

AU - Soelberg Sorensen, Per

AU - Spurkland, Anne

AU - Stankovich, Jim

AU - Stewart, Graeme

AU - Taylor, Bruce

AU - Ticca, Anna

AU - West, Sandra

AU - Zipp, Frauke

AU - Donnelly, Peter

AU - Barroso, Ines

AU - Blackwell, Jenefer M

AU - Bramon, Elvira

AU - Brown, Matthew A

AU - Casas, Juan P

AU - Corvin, Aiden

AU - Jankowski, Janusz

AU - Markus, Hugh S

AU - Mathew, Christopher G

AU - Palmer, Colin N A

AU - Plomin, Robert

AU - Rautanen, Anna

AU - Sawcer, Stephen

AU - Trembath, Richard C

AU - Viswanathan, Ananth C

AU - Wood, Nicholas W

AU - Spencer, Chris C A

AU - Band, Gavin

AU - Bellenguez, Céline

AU - Freeman, Colin

AU - Hellenthal, Garrett

AU - Giannoulatou, Eleni

AU - Pirinen, Matti

AU - Pearson, Richard

AU - Strange, Amy

AU - Su, Zhan

AU - Vukcevic, Damjan

AU - Donnelly, Peter

AU - Langford, Cordelia

AU - Hunt, Sarah E

AU - Edkins, Sarah

AU - Gwilliam, Rhian

AU - Blackburn, Hannah

AU - Bumpstead, Suzannah J

AU - Dronov, Serge

AU - Gillman, Matthew

AU - Gray, Emma

AU - Hammond, Naomi

AU - Jayakumar, Alagurevathi

AU - Mccann, Owen T

AU - Liddle, Jennifer

AU - Potter, Simon C

AU - Ravindrarajah, Rathi

AU - Ricketts, Michelle

AU - Waller, Matthew J

AU - Weston, Paul

AU - Widaa, Sara

AU - Whittaker, Pamela

AU - Barroso, Ines

AU - Deloukas, Panos

AU - Dilthey, Alexander

AU - Leslie, Stephen

AU - Moutsianas, Loukas

AU - Perez, Marc L

AU - Mcvean, Gil

AU - Mathew, Christopher G

AU - Blackwell, Jenefer M

AU - Brown, Matthew A

AU - Corvin, Aiden

AU - Mccarthy, Mark I

AU - Spencer, Chris C A

AU - De Jager, P L

AU - Baranzini, S E

AU - Cournu-rebeix, I

AU - Fontaine, B

PY - 2014/3

Y1 - 2014/3

N2 - 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.

AB - 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.

KW - Multiple sclerosis

KW - Susceptibility

KW - Pathway analysis

KW - Cell adhesion

KW - Molecules

U2 - 10.1038/gene.2013.70

DO - 10.1038/gene.2013.70

M3 - Article

SN - 1466-4879

VL - 15

SP - 126

EP - 132

JO - GENES AND IMMUNITY

JF - GENES AND IMMUNITY

IS - 2

M1 - N/A

ER -

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

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