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A "candidate-interactome" aggregate analysis of genome-wide association data in multiple sclerosis

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Mechelli, R and Umeton, R and Policano, C and Annibali, V and Coarelli, G and Ricigliano, VAG and Vittori, D and Fornasiero, A and Buscarinu, MC and Romano, S and Salvetti, M and Ristori, G and Sawcer, S and Hellenthal, G and Pirinen, M and Spencer, CCA and Patsopoulos, NA and Moutsianas, L and Dilthey, A and Su, Z and Freeman, C and Hunt, SE and Edkins, S and Gray, E and Booth, DR and Potter, SC and Goris, A and Band, G and Oturai, AB and Strange, A and Saarela, J and Bellenguez, C and Fontaine, B and Gillman, M and Hemmer, B and Gwilliam, R and Zipp, F and Jayakumar, A and Martin, R and Leslie, S and Hawkins, S and Giannoulatou, E and D'alfonso, S and Blackburn, H and Boneschi, FM and Liddle, J and Harbo, HF and Perez, ML and Spurkland, A and Waller, MJ and Mycko, MP and Ricketts, M and Comabella, M and Hammond, N and Kockum, I and McCann, OT and Ban, M and Whittaker, P and Kemppinen, A and Weston, P and Hawkins, C and Widaa, S and Zajicek, J and Dronov, S and Robertson, N and Bumpstead, SJ and Barcellos, LF and Ravindrarajah, R and Abraham, R and Alfredsson, L and Ardlie, K and Aubin, C and Baker, A and Baker, K and Baranzini, SE and Bergamaschi, L and Bergamaschi, R and Bernstein, A and Berthele, A and Boggild, M and Bradfield, JP and Brassat, D and Broadley, SA and Buck, D and Butzkueven, H and Capra, R and Carroll, WM and Cavalla, P and Celius, EG and Cepok, S and Chiavacci, R and Clerget-Darpoux, R and Clysters, K and Comi, G and Cossburn, M and Cournu-Rebeix, I and Cox, MB and Cozen, W and Cree, BAC and Cross, AH and Cusi, D and Daly, MJ and Davis, E and de Bakker, PIW and Debouverie, M and D'hooghe, B and Dixon, K and Dobosi, R and Dubois, B and Ellinghaus, D and Elovaara, I and Esposito, F and Fontenille, C and Foote, S and Franke, A and Galimberti, D and Ghezzi, A and Glessner, J and Gomez, R and Gout, O and Graham, C and Grant, SFA and Guerini, FR and Hakonarson, H and Hall, P and Hamsten, A and Hartung, HP and Heard, RN and Heath, S and Hobart, J and Hoshi, M and Infante-Duarte, C and Ingram, G and Ingram, W and Islam, T and Jagodic, M and Kabesch, M and Kermode, AG and Kilpatrick, TJ and Kim, C and Klopp, N and Koivisto, K and Larsson, M and Lathrop, M and Lechner-Scott, JS and Leone, MA and Leppa, V and Liljedahl, U and Bomfim, IL and Lincoln, RR and Link, J and Liu, J and Lorentzen, AR and Lupoli, S and Macciardi, F and Mack, T and Marriott, M and Martinelli, V and Mason, D and McCauley, JL and Mentch, F and Mero, IL and Mihalova, T and Montalban, X and Mottershead, J and Myhr, KM and Naldi, P and Ollier, W and Page, A and Palotie, A and Pelletier, J and Piccio, L and Pickersgill, T and Piehl, F and Pobywajlo, S and Quach, HL and Ramsay, PP and Reunanen, M and Reynolds, R and Rioux, JD and Rodegher, M and Roesner, S and Rubio, JP and Ruckert, IM and Salvi, E and Santaniello, A and Schaefer, CA and Schreiber, S and Schulze, C and Scott, RJ and Sellebjerg, F and Selmaj, KW and Sexton, D and Shen, L and Simms-Acuna, B and Skidmore, S and Sleiman, PMA and Smestad, C and Sorensen, PS and Sondergaard, HB and Stankovich, J and Strange, RC and Sulonen, AM and Sundqvist, E and Syvanen, AC and Taddeo, F and Taylor, B and Blackwell, JM and Tienari, P and Bramon, E and Tourbah, A and Brown, MA and Tronczynska, E and Casas, JP and Tubridy, N and Corvin, A and Vickery, J and Jankowski, J and Villoslada, P and Markus, HS and Wang, K and Mathew, CG and Wason, J and Palmer, CNA and Wichmann, HE and Plomin, R and Willoughby, E and Rautanen, A and Winkelmann, J and Wittig, M and Trembath, RC and Yaouanq, J and Viswanathan, AC and Zhang, H and Wood, NW and Zuvich, R and Deloukas, P and Langford, C and Duncanson, A and Oksenberg, JR and Pericak-Vance, MA and Haines, JL and Olsson, T and Hillert, J and Ivinson, AJ and De Jager, PL and Peltonen, L and Stewart, GJ and Hafler, DA and Hauser, SL and McVean, G and Donnelly, P and Compston, A, International Multiple Sclerosis Genetics Consortium, Wellcome Trust Case Control Consortium, A "candidate-interactome" aggregate analysis of genome-wide association data in multiple sclerosis, PLoS One, 8, (5) Article e63300. ISSN 1932-6203 (2013) [Refereed Article]


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Licenced under Creative Commons Attribution 2.5 Generic (CC BY 2.5) http://creativecommons.org/licenses/by/2.5/

DOI: doi:10.1371/journal.pone.0063300

Abstract

Though difficult, the study of gene-environment interactions in multifactorial diseases is crucial for interpreting the relevance of non-heritable factors and prevents from overlooking genetic associations with small but measurable effects. We propose a "candidate interactome" (i.e. a group of genes whose products are known to physically interact with environmental factors that may be relevant for disease pathogenesis) analysis of genome-wide association data in multiple sclerosis. We looked for statistical enrichment of associations among interactomes that, at the current state of knowledge, may be representative of gene-environment interactions of potential, uncertain or unlikely relevance for multiple sclerosis pathogenesis: Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, HHV8-Kaposi sarcoma, H1N1-influenza, JC virus, human innate immunity interactome for type I interferon, autoimmune regulator, vitamin D receptor, aryl hydrocarbon receptor and a panel of proteins targeted by 70 innate immune-modulating viral open reading frames from 30 viral species. Interactomes were either obtained from the literature or were manually curated. The P values of all single nucleotide polymorphism mapping to a given interactome were obtained from the last genome-wide association study of the International Multiple Sclerosis Genetics Consortium & the Wellcome Trust Case Control Consortium, 2. The interaction between genotype and Epstein Barr virus emerges as relevant for multiple sclerosis etiology. However, in line with recent data on the coexistence of common and unique strategies used by viruses to perturb the human molecular system, also other viruses have a similar potential, though probably less relevant in epidemiological terms.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Central Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Foote, S (Professor Simon Foote)
Author:Stankovich, J (Dr Jim Stankovich)
Author:Taylor, B (Professor Bruce Taylor)
ID Code:85544
Year Published:2013
Web of Science® Times Cited:17
Deposited By:Menzies Institute for Medical Research
Deposited On:2013-07-17
Last Modified:2017-11-07
Downloads:185 View Download Statistics

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