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

Rosella Mechelli, Renato Umeton, Claudia Policano, Viviana Annibali, Giulia Coarelli, Vito A G Ricigliano, Danila Vittori, Arianna Fornasiero, Maria Chiara Buscarinu, Silvia Romano, Marco Salvetti, Giovanni Ristori, Stephen Sawcer, Garrett Hellenthal, Matti Pirinen, Chris C A Spencer, Nikolaos A. Patsopoulos, Loukas Moutsianas, Alexander Dilthey, Zhan SuColin Freeman, Sarah E. Hunt, Sarah Edkins, Emma Gray, David R. Booth, Simon C. Potter, An Goris, Gavin Band, Annette Bang Oturai, Amy Strange, Janna Saarela, Céline Bellenguez, Bertrand Fontaine, Matthew Gillman, Bernhard Hemmer, Rhian Gwilliam, Frauke Zipp, Alagurevathi Jayakumar, Roland Martin, Stephen Leslie, Stanley Hawkins, Eleni Giannoulatou, Sandra D'alfonso, Hannah Blackburn, Filippo Martinelli Boneschi, Jennifer Liddle, Hanne F. Harbo, Marc L. Perez, Anne Spurkland, Matthew J. Waller, Marcin P. Mycko, Michelle Ricketts, Manuel Comabella, Naomi Hammond, Ingrid Kockum, Owen T. McCann, Maria Ban, Pamela Whittaker, Anu Kemppinen, Paul Weston, Clive Hawkins, Sara Widaa, John Zajicek, Serge Dronov, Neil Robertson, Suzannah J. Bumpstead, Lisa F. Barcellos, Rathi Ravindrarajah, Roby Abraham, Lars Alfredsson, Kristin Ardlie, Cristin Aubin, Amie Baker, Katharine Baker, Sergio E. Baranzini, Laura Bergamaschi, Roberto Bergamaschi, Allan Bernstein, Achim Berthele, Mike Boggild, Jonathan P. Bradfield, David Brassat, Simon A. Broadley, Dorothea Buck, Helmut Butzkueven, Ruggero Capra, William M. Carroll, Paola Cavalla, Elisabeth G. Celius, Sabine Cepok, Rosetta Chiavacci, Françoise Clerget-Darpoux, Katleen Clysters, Giancarlo Comi, Mark Cossburn, Isabelle Cournu-Rebeix, Mathew B. Cox, Wendy Cozen, Bruce A C Cree, Anne H. Cross, Daniele Cusi, Mark J. Daly, Emma Davis, Paul I W de Bakker, Marc Debouverie, Marie Beatrice D'hooghe, Katherine Dixon, Rita Dobosi, Bénédicte Dubois, David Ellinghaus, Irina Elovaara, Federica Esposito, Claire Fontenille, Simon Foote, Andre Franke, Daniela Galimberti, Angelo Ghezzi, Joseph Glessner, Refujia Gomez, Olivier Gout, Colin Graham, Struan F A Grant, Franca Rosa Guerini, Hakon Hakonarson, Per Hall, Anders Hamsten, Hans Peter Hartung, Rob N. Heard, Simon Heath, Jeremy Hobart, Muna Hoshi, Carmen Infante-Duarte, Gillian Ingram, Wendy Ingram, Talat Islam, Maja Jagodic, Michael Kabesch, Allan G. Kermode, Trevor J. Kilpatrick, Cecilia Kim, Norman Klopp, Keijo Koivisto, Malin Larsson, Mark Lathrop, Jeannette S. Lechner-Scott, Maurizio A. Leone, Virpi Leppä, Ulrika Liljedahl, Izaura Lima Bomfim, Robin R. Lincoln, Jenny Link, Jianjun Liu, Åslaug R. Lorentzen, Sara Lupoli, Fabio Macciardi, Thomas Mack, Mark Marriott, Vittorio Martinelli, Deborah Mason, Jacob L McCauley, Frank Mentch, Inger Lise Mero, Tania Mihalova, Xavier Montalban, John Mottershead, Kjell Morten Myhr, Paola Naldi, William Ollier, Alison Page, Aarno Palotie, Jean Pelletier, Laura Piccio, Trevor Pickersgill, Fredrik Piehl, Susan Pobywajlo, Hong L. Quach, Patricia P. Ramsay, Mauri Reunanen, Richard Reynolds, John D. Rioux, Mariaemma Rodegher, Sabine Roesner, Justin P. Rubio, Ina Maria Rückert, Erika Salvi, Adam Santaniello, Catherine A. Schaefer, Stefan Schreiber, Christian Schulze, Rodney J. Scott, Finn Sellebjerg, Krzysztof W. Selmaj, David Sexton, Ling Shen, Brigid Simms-Acuna, Sheila Skidmore, Patrick M A Sleiman, Cathrine Smestad, Per Soelberg Sørensen, Helle Bach Søndergaard, Jim Stankovich, Richard C. Strange, Anna Maija Sulonen, Emilie Sundqvist, Ann Christine Syvänen, Francesca Taddeo, Bruce Taylor, Jenefer M. Blackwell, Pentti Tienari, Elvira Bramon, Ayman Tourbah, Matthew A. Brown, Ewa Tronczynska, Juan P. Casas, Niall Tubridy, Aiden Corvin, Jane Vickery, Janusz Jankowski, Pablo Villoslada, Hugh S. Markus, Kai Wang, Christopher G. Mathew, James Wason, Colin N A Palmer, H. Erich Wichmann, Robert Plomin, Ernest Willoughby, Anna Rautanen, Juliane Winkelmann, Michael Wittig, Richard C. Trembath, Jacqueline Yaouanq, Ananth C. Viswanathan, Haitao Zhang, Nicholas W. Wood, Rebecca Zuvich, Panos Deloukas, Cordelia Langford, Audrey Duncanson, Jorge R. Oksenberg, Margaret A Pericak-Vance, Jonathan L. Haines, Tomas Olsson, Jan Hillert, Adrian J. Ivinson, Philip L. De Jager, Leena Peltonen, Graeme J. Stewart, David A. Hafler, Stephen L. Hauser, Gil McVean, Peter Donnelly, Alastair Compston

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish
Article numbere63300
JournalPLoS One
Volume8
Issue number5
DOIs
StatePublished - May 16 2013

Fingerprint

Genome-Wide Association Study
sclerosis
protein aggregates
Viruses
Multiple Sclerosis
Genes
Human herpesvirus 4
Gene-Environment Interaction
genotype-environment interaction
Human Herpesvirus 4
Nucleotide Mapping
JC polyomavirus
pathogenesis
JC Virus
Aryl Hydrocarbon Receptors
Cytomegalovirus
viruses
Interferon Type I
receptors
Calcitriol Receptors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Mechelli, R., Umeton, R., Policano, C., Annibali, V., Coarelli, G., Ricigliano, V. A. G., ... Compston, A. (2013). A "Candidate-Interactome" Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis. PLoS One, 8(5), [e63300]. https://doi.org/10.1371/journal.pone.0063300

A "Candidate-Interactome" Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis. / Mechelli, Rosella; Umeton, Renato; Policano, Claudia; Annibali, Viviana; Coarelli, Giulia; Ricigliano, Vito A G; Vittori, Danila; Fornasiero, Arianna; Buscarinu, Maria Chiara; Romano, Silvia; Salvetti, Marco; Ristori, Giovanni; Sawcer, Stephen; Hellenthal, Garrett; Pirinen, Matti; Spencer, Chris C A; Patsopoulos, Nikolaos A.; Moutsianas, Loukas; Dilthey, Alexander; Su, Zhan; Freeman, Colin; Hunt, Sarah E.; Edkins, Sarah; Gray, Emma; Booth, David R.; Potter, Simon C.; Goris, An; Band, Gavin; Oturai, Annette Bang; Strange, Amy; Saarela, Janna; Bellenguez, Céline; Fontaine, Bertrand; Gillman, Matthew; Hemmer, Bernhard; Gwilliam, Rhian; Zipp, Frauke; Jayakumar, Alagurevathi; Martin, Roland; Leslie, Stephen; Hawkins, Stanley; Giannoulatou, Eleni; D'alfonso, Sandra; Blackburn, Hannah; Boneschi, Filippo Martinelli; Liddle, Jennifer; Harbo, Hanne F.; Perez, Marc L.; Spurkland, Anne; Waller, Matthew J.; Mycko, Marcin P.; Ricketts, Michelle; Comabella, Manuel; Hammond, Naomi; Kockum, Ingrid; McCann, Owen T.; Ban, Maria; Whittaker, Pamela; Kemppinen, Anu; Weston, Paul; Hawkins, Clive; Widaa, Sara; Zajicek, John; Dronov, Serge; Robertson, Neil; Bumpstead, Suzannah J.; Barcellos, Lisa F.; Ravindrarajah, Rathi; Abraham, Roby; Alfredsson, Lars; Ardlie, Kristin; Aubin, Cristin; Baker, Amie; Baker, Katharine; Baranzini, Sergio E.; Bergamaschi, Laura; Bergamaschi, Roberto; Bernstein, Allan; Berthele, Achim; Boggild, Mike; Bradfield, Jonathan P.; Brassat, David; Broadley, Simon A.; Buck, Dorothea; Butzkueven, Helmut; Capra, Ruggero; Carroll, William M.; Cavalla, Paola; Celius, Elisabeth G.; Cepok, Sabine; Chiavacci, Rosetta; Clerget-Darpoux, Françoise; Clysters, Katleen; Comi, Giancarlo; Cossburn, Mark; Cournu-Rebeix, Isabelle; Cox, Mathew B.; Cozen, Wendy; Cree, Bruce A C; Cross, Anne H.; Cusi, Daniele; Daly, Mark J.; Davis, Emma; de Bakker, Paul I W; Debouverie, Marc; D'hooghe, Marie Beatrice; Dixon, Katherine; Dobosi, Rita; Dubois, Bénédicte; Ellinghaus, David; Elovaara, Irina; Esposito, Federica; Fontenille, Claire; Foote, Simon; Franke, Andre; Galimberti, Daniela; Ghezzi, Angelo; Glessner, Joseph; Gomez, Refujia; Gout, Olivier; Graham, Colin; Grant, Struan F A; Guerini, Franca Rosa; Hakonarson, Hakon; Hall, Per; Hamsten, Anders; Hartung, Hans Peter; Heard, Rob N.; Heath, Simon; Hobart, Jeremy; Hoshi, Muna; Infante-Duarte, Carmen; Ingram, Gillian; Ingram, Wendy; Islam, Talat; Jagodic, Maja; Kabesch, Michael; Kermode, Allan G.; Kilpatrick, Trevor J.; Kim, Cecilia; Klopp, Norman; Koivisto, Keijo; Larsson, Malin; Lathrop, Mark; Lechner-Scott, Jeannette S.; Leone, Maurizio A.; Leppä, Virpi; Liljedahl, Ulrika; Bomfim, Izaura Lima; Lincoln, Robin R.; Link, Jenny; Liu, Jianjun; Lorentzen, Åslaug R.; Lupoli, Sara; Macciardi, Fabio; Mack, Thomas; Marriott, Mark; Martinelli, Vittorio; Mason, Deborah; McCauley, Jacob L; Mentch, Frank; Mero, Inger Lise; Mihalova, Tania; Montalban, Xavier; Mottershead, John; Myhr, Kjell Morten; Naldi, Paola; Ollier, William; Page, Alison; Palotie, Aarno; Pelletier, Jean; Piccio, Laura; Pickersgill, Trevor; Piehl, Fredrik; Pobywajlo, Susan; Quach, Hong L.; Ramsay, Patricia P.; Reunanen, Mauri; Reynolds, Richard; Rioux, John D.; Rodegher, Mariaemma; Roesner, Sabine; Rubio, Justin P.; Rückert, Ina Maria; Salvi, Erika; Santaniello, Adam; Schaefer, Catherine A.; Schreiber, Stefan; Schulze, Christian; Scott, Rodney J.; Sellebjerg, Finn; Selmaj, Krzysztof W.; Sexton, David; Shen, Ling; Simms-Acuna, Brigid; Skidmore, Sheila; Sleiman, Patrick M A; Smestad, Cathrine; Sørensen, Per Soelberg; Søndergaard, Helle Bach; Stankovich, Jim; Strange, Richard C.; Sulonen, Anna Maija; Sundqvist, Emilie; Syvänen, Ann Christine; Taddeo, Francesca; Taylor, Bruce; Blackwell, Jenefer M.; Tienari, Pentti; Bramon, Elvira; Tourbah, Ayman; Brown, Matthew A.; Tronczynska, Ewa; Casas, Juan P.; Tubridy, Niall; Corvin, Aiden; Vickery, Jane; Jankowski, Janusz; Villoslada, Pablo; Markus, Hugh S.; Wang, Kai; Mathew, Christopher G.; Wason, James; Palmer, Colin N A; Wichmann, H. Erich; Plomin, Robert; Willoughby, Ernest; Rautanen, Anna; Winkelmann, Juliane; Wittig, Michael; Trembath, Richard C.; Yaouanq, Jacqueline; Viswanathan, Ananth C.; Zhang, Haitao; Wood, Nicholas W.; Zuvich, Rebecca; Deloukas, Panos; Langford, Cordelia; Duncanson, Audrey; Oksenberg, Jorge R.; Pericak-Vance, Margaret A; Haines, Jonathan L.; Olsson, Tomas; Hillert, Jan; Ivinson, Adrian J.; De Jager, Philip L.; Peltonen, Leena; Stewart, Graeme J.; Hafler, David A.; Hauser, Stephen L.; McVean, Gil; Donnelly, Peter; Compston, Alastair.

In: PLoS One, Vol. 8, No. 5, e63300, 16.05.2013.

Research output: Contribution to journalArticle

Mechelli, R, Umeton, R, Policano, C, Annibali, V, Coarelli, G, Ricigliano, VAG, Vittori, D, Fornasiero, A, Buscarinu, MC, Romano, S, Salvetti, M, Ristori, G, Sawcer, S, Hellenthal, G, Pirinen, M, Spencer, CCA, Patsopoulos, NA, Moutsianas, L, Dilthey, A, Su, Z, Freeman, C, Hunt, SE, Edkins, S, Gray, E, Booth, DR, Potter, SC, Goris, A, Band, G, Oturai, AB, 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, FM, Liddle, J, Harbo, HF, Perez, ML, Spurkland, A, Waller, MJ, Mycko, MP, Ricketts, M, Comabella, M, Hammond, N, Kockum, I, McCann, OT, Ban, M, Whittaker, P, Kemppinen, A, Weston, P, Hawkins, C, Widaa, S, Zajicek, J, Dronov, S, Robertson, N, Bumpstead, SJ, Barcellos, LF, Ravindrarajah, R, Abraham, R, Alfredsson, L, Ardlie, K, Aubin, C, Baker, A, Baker, K, Baranzini, SE, Bergamaschi, L, Bergamaschi, R, Bernstein, A, Berthele, A, Boggild, M, Bradfield, JP, Brassat, D, Broadley, SA, Buck, D, Butzkueven, H, Capra, R, Carroll, WM, Cavalla, P, Celius, EG, Cepok, S, Chiavacci, R, Clerget-Darpoux, F, Clysters, K, Comi, G, Cossburn, M, Cournu-Rebeix, I, Cox, MB, Cozen, W, Cree, BAC, Cross, AH, Cusi, D, Daly, MJ, Davis, E, de Bakker, PIW, Debouverie, M, D'hooghe, MB, 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, SFA, Guerini, FR, Hakonarson, H, Hall, P, Hamsten, A, Hartung, HP, Heard, RN, Heath, S, Hobart, J, Hoshi, M, Infante-Duarte, C, Ingram, G, Ingram, W, Islam, T, Jagodic, M, Kabesch, M, Kermode, AG, Kilpatrick, TJ, Kim, C, Klopp, N, Koivisto, K, Larsson, M, Lathrop, M, Lechner-Scott, JS, Leone, MA, Leppä, V, Liljedahl, U, Bomfim, IL, Lincoln, RR, Link, J, Liu, J, Lorentzen, ÅR, Lupoli, S, Macciardi, F, Mack, T, Marriott, M, Martinelli, V, Mason, D, McCauley, JL, Mentch, F, Mero, IL, Mihalova, T, Montalban, X, Mottershead, J, Myhr, KM, Naldi, P, Ollier, W, Page, A, Palotie, A, Pelletier, J, Piccio, L, Pickersgill, T, Piehl, F, Pobywajlo, S, Quach, HL, Ramsay, PP, Reunanen, M, Reynolds, R, Rioux, JD, Rodegher, M, Roesner, S, Rubio, JP, Rückert, IM, Salvi, E, Santaniello, A, Schaefer, CA, Schreiber, S, Schulze, C, Scott, RJ, Sellebjerg, F, Selmaj, KW, Sexton, D, Shen, L, Simms-Acuna, B, Skidmore, S, Sleiman, PMA, Smestad, C, Sørensen, PS, Søndergaard, HB, Stankovich, J, Strange, RC, Sulonen, AM, Sundqvist, E, Syvänen, AC, Taddeo, F, Taylor, B, Blackwell, JM, Tienari, P, Bramon, E, Tourbah, A, Brown, MA, Tronczynska, E, Casas, JP, Tubridy, N, Corvin, A, Vickery, J, Jankowski, J, Villoslada, P, Markus, HS, Wang, K, Mathew, CG, Wason, J, Palmer, CNA, Wichmann, HE, Plomin, R, Willoughby, E, Rautanen, A, Winkelmann, J, Wittig, M, Trembath, RC, Yaouanq, J, Viswanathan, AC, Zhang, H, Wood, NW, Zuvich, R, Deloukas, P, Langford, C, Duncanson, A, Oksenberg, JR, Pericak-Vance, MA, Haines, JL, Olsson, T, Hillert, J, Ivinson, AJ, De Jager, PL, Peltonen, L, Stewart, GJ, Hafler, DA, Hauser, SL, McVean, G, Donnelly, P & Compston, A 2013, 'A "Candidate-Interactome" Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis', PLoS One, vol. 8, no. 5, e63300. https://doi.org/10.1371/journal.pone.0063300
Mechelli R, Umeton R, Policano C, Annibali V, Coarelli G, Ricigliano VAG et al. A "Candidate-Interactome" Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis. PLoS One. 2013 May 16;8(5). e63300. https://doi.org/10.1371/journal.pone.0063300
Mechelli, Rosella ; Umeton, Renato ; Policano, Claudia ; Annibali, Viviana ; Coarelli, Giulia ; Ricigliano, Vito A G ; Vittori, Danila ; Fornasiero, Arianna ; Buscarinu, Maria Chiara ; Romano, Silvia ; Salvetti, Marco ; Ristori, Giovanni ; Sawcer, Stephen ; Hellenthal, Garrett ; Pirinen, Matti ; Spencer, Chris C A ; Patsopoulos, Nikolaos A. ; Moutsianas, Loukas ; Dilthey, Alexander ; Su, Zhan ; Freeman, Colin ; Hunt, Sarah E. ; Edkins, Sarah ; Gray, Emma ; Booth, David R. ; Potter, Simon C. ; Goris, An ; Band, Gavin ; Oturai, Annette Bang ; Strange, Amy ; Saarela, Janna ; Bellenguez, Céline ; Fontaine, Bertrand ; Gillman, Matthew ; Hemmer, Bernhard ; Gwilliam, Rhian ; Zipp, Frauke ; Jayakumar, Alagurevathi ; Martin, Roland ; Leslie, Stephen ; Hawkins, Stanley ; Giannoulatou, Eleni ; D'alfonso, Sandra ; Blackburn, Hannah ; Boneschi, Filippo Martinelli ; Liddle, Jennifer ; Harbo, Hanne F. ; Perez, Marc L. ; Spurkland, Anne ; Waller, Matthew J. ; Mycko, Marcin P. ; Ricketts, Michelle ; Comabella, Manuel ; Hammond, Naomi ; Kockum, Ingrid ; McCann, Owen T. ; Ban, Maria ; Whittaker, Pamela ; Kemppinen, Anu ; Weston, Paul ; Hawkins, Clive ; Widaa, Sara ; Zajicek, John ; Dronov, Serge ; Robertson, Neil ; Bumpstead, Suzannah J. ; Barcellos, Lisa F. ; Ravindrarajah, Rathi ; Abraham, Roby ; Alfredsson, Lars ; Ardlie, Kristin ; Aubin, Cristin ; Baker, Amie ; Baker, Katharine ; Baranzini, Sergio E. ; Bergamaschi, Laura ; Bergamaschi, Roberto ; Bernstein, Allan ; Berthele, Achim ; Boggild, Mike ; Bradfield, Jonathan P. ; Brassat, David ; Broadley, Simon A. ; Buck, Dorothea ; Butzkueven, Helmut ; Capra, Ruggero ; Carroll, William M. ; Cavalla, Paola ; Celius, Elisabeth G. ; Cepok, Sabine ; Chiavacci, Rosetta ; Clerget-Darpoux, Françoise ; Clysters, Katleen ; Comi, Giancarlo ; Cossburn, Mark ; Cournu-Rebeix, Isabelle ; Cox, Mathew B. ; Cozen, Wendy ; Cree, Bruce A C ; Cross, Anne H. ; Cusi, Daniele ; Daly, Mark J. ; Davis, Emma ; de Bakker, Paul I W ; Debouverie, Marc ; D'hooghe, Marie Beatrice ; Dixon, Katherine ; Dobosi, Rita ; Dubois, Bénédicte ; Ellinghaus, David ; Elovaara, Irina ; Esposito, Federica ; Fontenille, Claire ; Foote, Simon ; Franke, Andre ; Galimberti, Daniela ; Ghezzi, Angelo ; Glessner, Joseph ; Gomez, Refujia ; Gout, Olivier ; Graham, Colin ; Grant, Struan F A ; Guerini, Franca Rosa ; Hakonarson, Hakon ; Hall, Per ; Hamsten, Anders ; Hartung, Hans Peter ; Heard, Rob N. ; Heath, Simon ; Hobart, Jeremy ; Hoshi, Muna ; Infante-Duarte, Carmen ; Ingram, Gillian ; Ingram, Wendy ; Islam, Talat ; Jagodic, Maja ; Kabesch, Michael ; Kermode, Allan G. ; Kilpatrick, Trevor J. ; Kim, Cecilia ; Klopp, Norman ; Koivisto, Keijo ; Larsson, Malin ; Lathrop, Mark ; Lechner-Scott, Jeannette S. ; Leone, Maurizio A. ; Leppä, Virpi ; Liljedahl, Ulrika ; Bomfim, Izaura Lima ; Lincoln, Robin R. ; Link, Jenny ; Liu, Jianjun ; Lorentzen, Åslaug R. ; Lupoli, Sara ; Macciardi, Fabio ; Mack, Thomas ; Marriott, Mark ; Martinelli, Vittorio ; Mason, Deborah ; McCauley, Jacob L ; Mentch, Frank ; Mero, Inger Lise ; Mihalova, Tania ; Montalban, Xavier ; Mottershead, John ; Myhr, Kjell Morten ; Naldi, Paola ; Ollier, William ; Page, Alison ; Palotie, Aarno ; Pelletier, Jean ; Piccio, Laura ; Pickersgill, Trevor ; Piehl, Fredrik ; Pobywajlo, Susan ; Quach, Hong L. ; Ramsay, Patricia P. ; Reunanen, Mauri ; Reynolds, Richard ; Rioux, John D. ; Rodegher, Mariaemma ; Roesner, Sabine ; Rubio, Justin P. ; Rückert, Ina Maria ; Salvi, Erika ; Santaniello, Adam ; Schaefer, Catherine A. ; Schreiber, Stefan ; Schulze, Christian ; Scott, Rodney J. ; Sellebjerg, Finn ; Selmaj, Krzysztof W. ; Sexton, David ; Shen, Ling ; Simms-Acuna, Brigid ; Skidmore, Sheila ; Sleiman, Patrick M A ; Smestad, Cathrine ; Sørensen, Per Soelberg ; Søndergaard, Helle Bach ; Stankovich, Jim ; Strange, Richard C. ; Sulonen, Anna Maija ; Sundqvist, Emilie ; Syvänen, Ann Christine ; Taddeo, Francesca ; Taylor, Bruce ; Blackwell, Jenefer M. ; Tienari, Pentti ; Bramon, Elvira ; Tourbah, Ayman ; Brown, Matthew A. ; Tronczynska, Ewa ; Casas, Juan P. ; Tubridy, Niall ; Corvin, Aiden ; Vickery, Jane ; Jankowski, Janusz ; Villoslada, Pablo ; Markus, Hugh S. ; Wang, Kai ; Mathew, Christopher G. ; Wason, James ; Palmer, Colin N A ; Wichmann, H. Erich ; Plomin, Robert ; Willoughby, Ernest ; Rautanen, Anna ; Winkelmann, Juliane ; Wittig, Michael ; Trembath, Richard C. ; Yaouanq, Jacqueline ; Viswanathan, Ananth C. ; Zhang, Haitao ; Wood, Nicholas W. ; Zuvich, Rebecca ; Deloukas, Panos ; Langford, Cordelia ; Duncanson, Audrey ; Oksenberg, Jorge R. ; Pericak-Vance, Margaret A ; Haines, Jonathan L. ; Olsson, Tomas ; Hillert, Jan ; Ivinson, Adrian J. ; De Jager, Philip L. ; Peltonen, Leena ; Stewart, Graeme J. ; Hafler, David A. ; Hauser, Stephen L. ; McVean, Gil ; Donnelly, Peter ; Compston, Alastair. / A "Candidate-Interactome" Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis. In: PLoS One. 2013 ; Vol. 8, No. 5.
@article{b79a3bde2b1a4ee2a5022eb0ecd51f5c,
title = "A {"}Candidate-Interactome{"} Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis",
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.",
author = "Rosella Mechelli and Renato Umeton and Claudia Policano and Viviana Annibali and Giulia Coarelli and Ricigliano, {Vito A G} and Danila Vittori and Arianna Fornasiero and Buscarinu, {Maria Chiara} and Silvia Romano and Marco Salvetti and Giovanni Ristori and Stephen Sawcer and Garrett Hellenthal and Matti Pirinen and Spencer, {Chris C A} and Patsopoulos, {Nikolaos A.} and Loukas Moutsianas and Alexander Dilthey and Zhan Su and Colin Freeman and Hunt, {Sarah E.} and Sarah Edkins and Emma Gray and Booth, {David R.} and Potter, {Simon C.} and An Goris and Gavin Band and Oturai, {Annette Bang} and Amy Strange and Janna Saarela and C{\'e}line Bellenguez and Bertrand Fontaine and Matthew Gillman and Bernhard Hemmer and Rhian Gwilliam and Frauke Zipp and Alagurevathi Jayakumar and Roland Martin and Stephen Leslie and Stanley Hawkins and Eleni Giannoulatou and Sandra D'alfonso and Hannah Blackburn and Boneschi, {Filippo Martinelli} and Jennifer Liddle and Harbo, {Hanne F.} and Perez, {Marc L.} and Anne Spurkland and Waller, {Matthew J.} and Mycko, {Marcin P.} and Michelle Ricketts and Manuel Comabella and Naomi Hammond and Ingrid Kockum and McCann, {Owen T.} and Maria Ban and Pamela Whittaker and Anu Kemppinen and Paul Weston and Clive Hawkins and Sara Widaa and John Zajicek and Serge Dronov and Neil Robertson and Bumpstead, {Suzannah J.} and Barcellos, {Lisa F.} and Rathi Ravindrarajah and Roby Abraham and Lars Alfredsson and Kristin Ardlie and Cristin Aubin and Amie Baker and Katharine Baker and Baranzini, {Sergio E.} and Laura Bergamaschi and Roberto Bergamaschi and Allan Bernstein and Achim Berthele and Mike Boggild and Bradfield, {Jonathan P.} and David Brassat and Broadley, {Simon A.} and Dorothea Buck and Helmut Butzkueven and Ruggero Capra and Carroll, {William M.} and Paola Cavalla and Celius, {Elisabeth G.} and Sabine Cepok and Rosetta Chiavacci and Fran{\cc}oise Clerget-Darpoux and Katleen Clysters and Giancarlo Comi and Mark Cossburn and Isabelle Cournu-Rebeix and Cox, {Mathew B.} and Wendy Cozen and Cree, {Bruce A C} and Cross, {Anne H.} and Daniele Cusi and Daly, {Mark J.} and Emma Davis and {de Bakker}, {Paul I W} and Marc Debouverie and D'hooghe, {Marie Beatrice} and Katherine Dixon and Rita Dobosi and B{\'e}n{\'e}dicte Dubois and David Ellinghaus and Irina Elovaara and Federica Esposito and Claire Fontenille and Simon Foote and Andre Franke and Daniela Galimberti and Angelo Ghezzi and Joseph Glessner and Refujia Gomez and Olivier Gout and Colin Graham and Grant, {Struan F A} and Guerini, {Franca Rosa} and Hakon Hakonarson and Per Hall and Anders Hamsten and Hartung, {Hans Peter} and Heard, {Rob N.} and Simon Heath and Jeremy Hobart and Muna Hoshi and Carmen Infante-Duarte and Gillian Ingram and Wendy Ingram and Talat Islam and Maja Jagodic and Michael Kabesch and Kermode, {Allan G.} and Kilpatrick, {Trevor J.} and Cecilia Kim and Norman Klopp and Keijo Koivisto and Malin Larsson and Mark Lathrop and Lechner-Scott, {Jeannette S.} and Leone, {Maurizio A.} and Virpi Lepp{\"a} and Ulrika Liljedahl and Bomfim, {Izaura Lima} and Lincoln, {Robin R.} and Jenny Link and Jianjun Liu and Lorentzen, {{\AA}slaug R.} and Sara Lupoli and Fabio Macciardi and Thomas Mack and Mark Marriott and Vittorio Martinelli and Deborah Mason and McCauley, {Jacob L} and Frank Mentch and Mero, {Inger Lise} and Tania Mihalova and Xavier Montalban and John Mottershead and Myhr, {Kjell Morten} and Paola Naldi and William Ollier and Alison Page and Aarno Palotie and Jean Pelletier and Laura Piccio and Trevor Pickersgill and Fredrik Piehl and Susan Pobywajlo and Quach, {Hong L.} and Ramsay, {Patricia P.} and Mauri Reunanen and Richard Reynolds and Rioux, {John D.} and Mariaemma Rodegher and Sabine Roesner and Rubio, {Justin P.} and R{\"u}ckert, {Ina Maria} and Erika Salvi and Adam Santaniello and Schaefer, {Catherine A.} and Stefan Schreiber and Christian Schulze and Scott, {Rodney J.} and Finn Sellebjerg and Selmaj, {Krzysztof W.} and David Sexton and Ling Shen and Brigid Simms-Acuna and Sheila Skidmore and Sleiman, {Patrick M A} and Cathrine Smestad and S{\o}rensen, {Per Soelberg} and S{\o}ndergaard, {Helle Bach} and Jim Stankovich and Strange, {Richard C.} and Sulonen, {Anna Maija} and Emilie Sundqvist and Syv{\"a}nen, {Ann Christine} and Francesca Taddeo and Bruce Taylor and Blackwell, {Jenefer M.} and Pentti Tienari and Elvira Bramon and Ayman Tourbah and Brown, {Matthew A.} and Ewa Tronczynska and Casas, {Juan P.} and Niall Tubridy and Aiden Corvin and Jane Vickery and Janusz Jankowski and Pablo Villoslada and Markus, {Hugh S.} and Kai Wang and Mathew, {Christopher G.} and James Wason and Palmer, {Colin N A} and Wichmann, {H. Erich} and Robert Plomin and Ernest Willoughby and Anna Rautanen and Juliane Winkelmann and Michael Wittig and Trembath, {Richard C.} and Jacqueline Yaouanq and Viswanathan, {Ananth C.} and Haitao Zhang and Wood, {Nicholas W.} and Rebecca Zuvich and Panos Deloukas and Cordelia Langford and Audrey Duncanson and Oksenberg, {Jorge R.} and Pericak-Vance, {Margaret A} and Haines, {Jonathan L.} and Tomas Olsson and Jan Hillert and Ivinson, {Adrian J.} and {De Jager}, {Philip L.} and Leena Peltonen and Stewart, {Graeme J.} and Hafler, {David A.} and Hauser, {Stephen L.} and Gil McVean and Peter Donnelly and Alastair Compston",
year = "2013",
month = "5",
day = "16",
doi = "10.1371/journal.pone.0063300",
language = "English",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "5",

}

TY - JOUR

T1 - A "Candidate-Interactome" Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis

AU - Mechelli, Rosella

AU - Umeton, Renato

AU - Policano, Claudia

AU - Annibali, Viviana

AU - Coarelli, Giulia

AU - Ricigliano, Vito A G

AU - Vittori, Danila

AU - Fornasiero, Arianna

AU - Buscarinu, Maria Chiara

AU - Romano, Silvia

AU - Salvetti, Marco

AU - Ristori, Giovanni

AU - Sawcer, Stephen

AU - Hellenthal, Garrett

AU - Pirinen, Matti

AU - Spencer, Chris C A

AU - Patsopoulos, Nikolaos A.

AU - Moutsianas, Loukas

AU - Dilthey, Alexander

AU - Su, Zhan

AU - Freeman, Colin

AU - Hunt, Sarah E.

AU - Edkins, Sarah

AU - Gray, Emma

AU - Booth, David R.

AU - Potter, Simon C.

AU - Goris, An

AU - Band, Gavin

AU - Oturai, Annette Bang

AU - Strange, Amy

AU - Saarela, Janna

AU - Bellenguez, Céline

AU - Fontaine, Bertrand

AU - Gillman, Matthew

AU - Hemmer, Bernhard

AU - Gwilliam, Rhian

AU - Zipp, Frauke

AU - Jayakumar, Alagurevathi

AU - Martin, Roland

AU - Leslie, Stephen

AU - Hawkins, Stanley

AU - Giannoulatou, Eleni

AU - D'alfonso, Sandra

AU - Blackburn, Hannah

AU - Boneschi, Filippo Martinelli

AU - Liddle, Jennifer

AU - Harbo, Hanne F.

AU - Perez, Marc L.

AU - Spurkland, Anne

AU - Waller, Matthew J.

AU - Mycko, Marcin P.

AU - Ricketts, Michelle

AU - Comabella, Manuel

AU - Hammond, Naomi

AU - Kockum, Ingrid

AU - McCann, Owen T.

AU - Ban, Maria

AU - Whittaker, Pamela

AU - Kemppinen, Anu

AU - Weston, Paul

AU - Hawkins, Clive

AU - Widaa, Sara

AU - Zajicek, John

AU - Dronov, Serge

AU - Robertson, Neil

AU - Bumpstead, Suzannah J.

AU - Barcellos, Lisa F.

AU - Ravindrarajah, Rathi

AU - Abraham, Roby

AU - Alfredsson, Lars

AU - Ardlie, Kristin

AU - Aubin, Cristin

AU - Baker, Amie

AU - Baker, Katharine

AU - Baranzini, Sergio E.

AU - Bergamaschi, Laura

AU - Bergamaschi, Roberto

AU - Bernstein, Allan

AU - Berthele, Achim

AU - Boggild, Mike

AU - Bradfield, Jonathan P.

AU - Brassat, David

AU - Broadley, Simon A.

AU - Buck, Dorothea

AU - Butzkueven, Helmut

AU - Capra, Ruggero

AU - Carroll, William M.

AU - Cavalla, Paola

AU - Celius, Elisabeth G.

AU - Cepok, Sabine

AU - Chiavacci, Rosetta

AU - Clerget-Darpoux, Françoise

AU - Clysters, Katleen

AU - Comi, Giancarlo

AU - Cossburn, Mark

AU - Cournu-Rebeix, Isabelle

AU - Cox, Mathew B.

AU - Cozen, Wendy

AU - Cree, Bruce A C

AU - Cross, Anne H.

AU - Cusi, Daniele

AU - Daly, Mark J.

AU - Davis, Emma

AU - de Bakker, Paul I W

AU - Debouverie, Marc

AU - D'hooghe, Marie Beatrice

AU - Dixon, Katherine

AU - Dobosi, Rita

AU - Dubois, Bénédicte

AU - Ellinghaus, David

AU - Elovaara, Irina

AU - Esposito, Federica

AU - Fontenille, Claire

AU - Foote, Simon

AU - Franke, Andre

AU - Galimberti, Daniela

AU - Ghezzi, Angelo

AU - Glessner, Joseph

AU - Gomez, Refujia

AU - Gout, Olivier

AU - Graham, Colin

AU - Grant, Struan F A

AU - Guerini, Franca Rosa

AU - Hakonarson, Hakon

AU - Hall, Per

AU - Hamsten, Anders

AU - Hartung, Hans Peter

AU - Heard, Rob N.

AU - Heath, Simon

AU - Hobart, Jeremy

AU - Hoshi, Muna

AU - Infante-Duarte, Carmen

AU - Ingram, Gillian

AU - Ingram, Wendy

AU - Islam, Talat

AU - Jagodic, Maja

AU - Kabesch, Michael

AU - Kermode, Allan G.

AU - Kilpatrick, Trevor J.

AU - Kim, Cecilia

AU - Klopp, Norman

AU - Koivisto, Keijo

AU - Larsson, Malin

AU - Lathrop, Mark

AU - Lechner-Scott, Jeannette S.

AU - Leone, Maurizio A.

AU - Leppä, Virpi

AU - Liljedahl, Ulrika

AU - Bomfim, Izaura Lima

AU - Lincoln, Robin R.

AU - Link, Jenny

AU - Liu, Jianjun

AU - Lorentzen, Åslaug R.

AU - Lupoli, Sara

AU - Macciardi, Fabio

AU - Mack, Thomas

AU - Marriott, Mark

AU - Martinelli, Vittorio

AU - Mason, Deborah

AU - McCauley, Jacob L

AU - Mentch, Frank

AU - Mero, Inger Lise

AU - Mihalova, Tania

AU - Montalban, Xavier

AU - Mottershead, John

AU - Myhr, Kjell Morten

AU - Naldi, Paola

AU - Ollier, William

AU - Page, Alison

AU - Palotie, Aarno

AU - Pelletier, Jean

AU - Piccio, Laura

AU - Pickersgill, Trevor

AU - Piehl, Fredrik

AU - Pobywajlo, Susan

AU - Quach, Hong L.

AU - Ramsay, Patricia P.

AU - Reunanen, Mauri

AU - Reynolds, Richard

AU - Rioux, John D.

AU - Rodegher, Mariaemma

AU - Roesner, Sabine

AU - Rubio, Justin P.

AU - Rückert, Ina Maria

AU - Salvi, Erika

AU - Santaniello, Adam

AU - Schaefer, Catherine A.

AU - Schreiber, Stefan

AU - Schulze, Christian

AU - Scott, Rodney J.

AU - Sellebjerg, Finn

AU - Selmaj, Krzysztof W.

AU - Sexton, David

AU - Shen, Ling

AU - Simms-Acuna, Brigid

AU - Skidmore, Sheila

AU - Sleiman, Patrick M A

AU - Smestad, Cathrine

AU - Sørensen, Per Soelberg

AU - Søndergaard, Helle Bach

AU - Stankovich, Jim

AU - Strange, Richard C.

AU - Sulonen, Anna Maija

AU - Sundqvist, Emilie

AU - Syvänen, Ann Christine

AU - Taddeo, Francesca

AU - Taylor, Bruce

AU - Blackwell, Jenefer M.

AU - Tienari, Pentti

AU - Bramon, Elvira

AU - Tourbah, Ayman

AU - Brown, Matthew A.

AU - Tronczynska, Ewa

AU - Casas, Juan P.

AU - Tubridy, Niall

AU - Corvin, Aiden

AU - Vickery, Jane

AU - Jankowski, Janusz

AU - Villoslada, Pablo

AU - Markus, Hugh S.

AU - Wang, Kai

AU - Mathew, Christopher G.

AU - Wason, James

AU - Palmer, Colin N A

AU - Wichmann, H. Erich

AU - Plomin, Robert

AU - Willoughby, Ernest

AU - Rautanen, Anna

AU - Winkelmann, Juliane

AU - Wittig, Michael

AU - Trembath, Richard C.

AU - Yaouanq, Jacqueline

AU - Viswanathan, Ananth C.

AU - Zhang, Haitao

AU - Wood, Nicholas W.

AU - Zuvich, Rebecca

AU - Deloukas, Panos

AU - Langford, Cordelia

AU - Duncanson, Audrey

AU - Oksenberg, Jorge R.

AU - Pericak-Vance, Margaret A

AU - Haines, Jonathan L.

AU - Olsson, Tomas

AU - Hillert, Jan

AU - Ivinson, Adrian J.

AU - De Jager, Philip L.

AU - Peltonen, Leena

AU - Stewart, Graeme J.

AU - Hafler, David A.

AU - Hauser, Stephen L.

AU - McVean, Gil

AU - Donnelly, Peter

AU - Compston, Alastair

PY - 2013/5/16

Y1 - 2013/5/16

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84877798701&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84877798701&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0063300

DO - 10.1371/journal.pone.0063300

M3 - Article

C2 - 23696811

AN - SCOPUS:84877798701

VL - 8

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 5

M1 - e63300

ER -