A "Candidate-Interactome" Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis

Mechelli, R., Umeton, R., Policano, C., Annibali, V., Coarelli, G., Ricigliano, V. A. G., Vittori, D., Fornasiero, A., Buscarinu, M. C., Romano, S., Salvetti, M., Ristori, G., Sawcer, S., Hellenthal, G., Pirinen, M., Spencer, C. C. A., Patsopoulos, N. A., Moutsianas, L., Dilthey, A., Su, Z., Freeman, C., Hunt, S. E., Edkins, S., Gray, E., Booth, D. R., Potter, S. C., Goris, A., Band, G., Oturai, A. B., Strange, A., Saarela, J., Bellenguez, C., Fontaine, B., Gillman, M., Hemmer, B., Gwilliam, R., Zipp, F., Jayakumar, A., Martin, R., Leslie, S., Hawkins, S., Giannoulatou, E., D'Alfonso, S., Blackburn, H., Boneschi, F. M., Liddle, J., Harbo, H. F., Perez, M. L., Spurkland, A., Waller, M. J., Mycko, M. P., Ricketts, M., Comabella, M., Hammond, N., Kockum, I., McCann, O. T., Ban, M., Whittaker, P., Kemppinen, A., Weston, P., Hawkins, C., Widaa, S., Zajicek, J., Dronov, S., Robertson, N., Bumpstead, S. J., Barcellos, L. F., Ravindrarajah, R., Abraham, R., Alfredsson, L., Ardlie, K., Aubin, C., Baker, A., Baker, K., Baranzini, S. E., Bergamaschi, L., Bergamaschi, R., Bernstein, A., Berthele, A., Boggild, M., Bradfield, J. P., Brassat, D., Broadley, S. A., Buck, D., Butzkueven, H., Capra, R., Carroll, W. M., Cavalla, P., Celius, E. G., Cepok, S., Chiavacci, R., Clerget-Darpoux, F., Clysters, K., Comi, G., Cossburn, M., Cournu-Rebeix, I., Cox, M. B., Cozen, W., Cree, B. A. C., Cross, A. H., Cusi, D., Daly, M. J., Davis, E., de Bakker, P. I. W., Debouverie, M., D'Hooghe, M. B., Dixon, K., Dobosi, R., Dubois, B., Ellinghaus, D., Elovaara, I., Esposito, F., Fontenille, C., Foote, S., Franke, A., Galimberti, D., Ghezzi, A., Glessner, J., Gomez, R., Gout, O., Graham, C., Grant, S. F. A., Guerini, F. R., Hakonarson, H., Hall, P., Hamsten, A., Hartung, H. P., Heard, R. N., Heath, S., Hobart, J., Hoshi, M., Infante-Duarte, C., Ingram, G., Ingram, W., Islam, T., Jagodic, M., Kabesch, M., Kermode, A. G., Kilpatrick, T. J., Kim, C., Klopp, N., Koivisto, K., Larsson, M., Lathrop, M., Lechner-Scott, J. S., Leone, M. A., Leppä, V., Liljedahl, U., Bomfim, I. L., Lincoln, R. R., Link, J., Liu, J., Lorentzen, Å R., Lupoli, S., Macciardi, F., Mack, T., Marriott, M., Martinelli, V., Mason, D., McCauley, J. L., Mentch, F., Mero, I. L., Mihalova, T., Montalban, X., Mottershead, J., Myhr, K. M., Naldi, P., Ollier, W., Page, A., Palotie, A., Pelletier, J., Piccio, L., Pickersgill, T., Piehl, F., Pobywajlo, S., Quach, H. L., Ramsay, P. P., Reunanen, M., Reynolds, R., Rioux, J. D., Rodegher, M., Roesner, S., Rubio, J. P., Rückert, I. M., Salvi, E., Santaniello, A., Schaefer, C. A., Schreiber, S., Schulze, C., Scott, R. J., Sellebjerg, F., Selmaj, K. W., Sexton, D., Shen, L., Simms-Acuna, B., Skidmore, S., Sleiman, P. M. A., Smestad, C., Sørensen, P. S., Søndergaard, H. B., Stankovich, J., Strange, R. C., Sulonen, A. M., Sundqvist, E., Syvänen, A. C., Taddeo, F., Taylor, B., Blackwell, J. M., Tienari, P., Bramon, E., Tourbah, A., Brown, M. A., Tronczynska, E., Casas, J. P., Tubridy, N., Corvin, A., Vickery, J., Jankowski, J., Villoslada, P., Markus, H. S., Wang, K., Mathew, C. G., Wason, J., Palmer, C. N. A., Wichmann, H. E., Plomin, R., Willoughby, E., Rautanen, A., Winkelmann, J., Wittig, M., Trembath, R. C., Yaouanq, J., Viswanathan, A. C., Zhang, H., Wood, N. W., Zuvich, R., Deloukas, P., Langford, C., Duncanson, A., Oksenberg, J. R., Pericak-Vance, M. A., Haines, J. L., Olsson, T., Hillert, J., Ivinson, A. J., De Jager, P. L., Peltonen, L., Stewart, G. J., Hafler, D. A., Hauser, S. L., McVean, G., Donnelly, P., & Compston, A. (2013) A "Candidate-Interactome" Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis. PLoS ONE, 8(5).

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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. © 2013 Mechelli et al.

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ID Code: 87618
Item Type: Journal Article
Refereed: Yes
Keywords: aromatic hydrocarbon receptor, autoimmune regulator protein, interferon, vitamin D receptor, article, Cytomegalovirus, Epstein Barr virus, gene mapping, genetic analysis, genetic association, genotype environment interaction, Hepatitis B virus, Hepatitis C virus, human, Human herpesvirus 8, Human immunodeficiency virus, influenza A (H1N1), innate immunity, JC virus, Kaposi sarcoma, multiple sclerosis, neuropathology, nonhuman, open reading frame, protein targeting, single nucleotide polymorphism, Genome-Wide Association Study, Genotype, Humans, Protein Binding
DOI: 10.1371/journal.pone.0063300
ISSN: 19326203 (ISSN)
Divisions: Current > Schools > School of Biomedical Sciences
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: The authors
Deposited On: 21 Sep 2015 07:06
Last Modified: 22 Feb 2016 04:32

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