التفاصيل البيبلوغرافية
العنوان:
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
المؤلفون:
Per Hall , Simon C. Potter , Richard Reynolds , Robert Heard , Gil McVean , An Goris , Joseph T. Glessner , Pamela Whittaker , Niall Tubridy , Olivier Gout , Ann-Christine Syvaenen , Leena Peltonen , Bénédicte Dubois , Anders Hamsten , Alastair Compston , Hugh S. Markus , Mariaemma Rodegher , Lisa F. Barcellos , Wendy Cozen , Rosetta M. Chiavacci , Jenefer M. Blackwell , William M. Carroll , Patricia P. Ramsay , Amie Baker , Krzysztof Selmaj , Serge Dronov , Zhan Su , C. Smestad , Stanley Hawkins , Janna Saarela , Matti Pirinen , Sabine Cepok , Gavin Band , Norman Klopp , Simon Heath , Sandra D'Alfonso , Peter Donnelly , Ina-Maria Rueckert , Deborah F. Mason , Alagurevathi Jayakumar , Hakon Hakonarson , Cecilia Kim , Colin Freeman , Jeannette Lechner-Scott , Marc Debouverie , Neil Robertson , Inger-Lise Mero , Paola Cavalla , Sabine Roesner , H-Erich Wichmann , Daniele Cusi , Wendy Ingram , Sarah Edkins , Tania Mihalova , Mark J. Daly , Mark Marriott , Roland Martin , Adrian J. Ivinson , Hong L. Quach , Jeremy Hobart , Filippo Martinelli Boneschi , Carmen Infante-Duarte , Catherine Schaefer , Irina Elovaara , Jonathan L. Haines , John Zajicek , Michelle Ricketts , Ananth C. Viswanathan , Colin A. Graham , Allan G. Kermode , Helmut Butzkueven , Kai Wang , John Mottershead , Francesca Taddeo , Stefan Schreiber , Aarno Palotie , Trevor Pickersgill , Naomi Hammond , David A. Hafler , Robert Plomin , Robin R. Lincoln , David Sexton , Jianjun Liu , Finn Sellebjerg , Françoise Clerget-Darpoux , David Brassat , Sarah E. Hunt , Per Soelberg Sørensen , Vittorio Martinelli , Eleni Giannoulatou , Paul I.W. de Bakker , Alexander T. Dilthey , Stephen Leslie , Ulrika Liljedahl , Hanne F. Harbo , Alison Page , Keijo Koivisto , Ingrid Kockum , Stephen L. Hauser , Ewa Tronczynska , Ayman Tourbah , K Baker , Panos Deloukas , Hannah Blackburn , Janusz Jankowski , Mauri Reunanen , Trevor J. Kilpatrick , Sheila Skidmore , Sergio E. Baranzini , Nicholas W. Wood , Fredrik Piehl , Lars Alfredsson , Daniela Galimberti , Federica Esposito , Marco Salvetti , Jennifer Liddle , Jenny Link , Helle Bach Søndergaard , Suzannah Bumpstead , Jonathan P. Bradfield , Richard C. Strange , Céline Bellenguez , David R. Booth , Refujia Gomez , Michael Wittig , Matthew A. Brown , Laura Bergamaschi , Elisabeth Gulowsen Celius , William E R Ollier , Juan P. Casas , Ling Shen , Loukas Moutsianas , Fabio Macciardi , Anne H. Cross , Maja Jagodic , Marie B. D'hooghe , Tomas Olsson , Mark D. Cossburn , O. T. McCann , Justin P. Rubio , Isabelle Cournu-Rebeix , Struan F.A. Grant , Colin N. A. Palmer , Matthew W. Gillman , John D. Rioux , Christopher G. Mathew , Maria Ban , Anna-Maija Sulonen , Garrett Hellenthal , Dorothea Buck , Jorge R. Oksenberg , Frauke Zipp , James Wason , Stephen Sawcer , Franca Rosa Guerini , Clive Hawkins , Cristin Aubin , Elvira Bramon , Paul A. Weston , Andre Franke , Laura Piccio , Jane Vickery , Nikolaos A. Patsopoulos , Jacob L. McCauley , Kristin G. Ardlie , A. Strange , Marcin P. Mycko , Richard C. Trembath , Giancarlo Comi , Gillian Ingram , Graeme J. Stewart , Allan L. Bernstein , Emilie Sundqvist , Xavier Montalban , Juliane Winkelmann , Rhian Gwilliam , Ruggero Capra , Bruce V. Taylor , Maurizio Leone , Brigid Simms-Acuna , Emma J. Davis , Bertrand Fontaine , Chris C. A. Spencer , Malin Larsson , Hans-Peter Hartung , Emma Gray , Virpi M. Leppä , Pablo Villoslada , Audrey Duncanson , Åslaug R. Lorentzen , Rathi Ravindrarajah , Izaura Lima Bomfim , Christian Schulze , Talat Islam , Manuel Comabella , Rita Dobosi , Simon Broadley , Bernhard Hemmer , Margaret A. Pericak-Vance , Jan Hillert , Michael Kabesch , J. Yaouanq , Mark Lathrop , Angelo Ghezzi , Rodney J. Scott , K Dixon , Jean Pelletier , Annette Bang Oturai , Mike Boggild , Philip L. De Jager , Anne Spurkland , M. Perez , Roby Abraham , Pentti J. Tienari , Matthew Waller , Katleen Clysters , Adam Santaniello , David Ellinghaus , Cordelia Langford , Anna Rautanen , Frank D. Mentch , Achim Berthele , Kjell-Morten Myhr , Simon J. Foote , Thomas M. Mack , Bruce A.C. Cree , Susan Pobywajlo , Ernest Willoughby , Haitao Zhang , M. B. Cox , Anu Kemppinen , Muna Hoshi , Sara Widaa , Claire Fontenille , Erika Salvi , Sara Lupoli , Aiden Corvin , Roberto Bergamaschi , Jim Stankovich , Rebecca L. Zuvich , Paola Naldi , Patrick M. A. Sleiman
المساهمون:
Clinical sciences, Neuroprotection & Neuromodulation, Neurology, Faculty of Psychology and Educational Sciences
المصدر:
Nature
سنة النشر:
2016
مصطلحات موضوعية:
Immunity, Cellular/genetics , Cellular immunity , Multiple Sclerosis , Genome-wide association study , CLEC16A , Biology , Polymorphism, Single Nucleotide , Cell Differentiation/immunology , Europe/ethnology , Major Histocompatibility Complex/genetics , Major Histocompatibility Complex , 03 medical and health sciences , 0302 clinical medicine , medicine , Genetic predisposition , Humans , Genetic Predisposition to Disease , HLA-A Antigens/genetics , Alleles , 030304 developmental biology , Genetic association , Genetics , 0303 health sciences , Immunity, Cellular , Multidisciplinary , HLA-A Antigens , Genome, Human , Multiple sclerosis , Genetic Predisposition to Disease/genetics , HLA-DR Antigens/genetics , Lymphocyte differentiation , Cell Differentiation , HLA-DR Antigens , T-Lymphocytes, Helper-Inducer , RC346 , medicine.disease , Polymorphism, Single Nucleotide/genetics , Genetic architecture , 3. Good health , Europe , Sample Size , Immunology , Genome, Human/genetics , Multiple Sclerosis/genetics , 030217 neurology & neurosurgery , T-Lymphocytes, Helper-Inducer/cytology , Genome-Wide Association Study , HLA-DRB1 Chains
الوصف:
Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
وصف الملف:
application/pdf
اللغة:
English
تدمد:
0028-0836
URL الوصول:
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::108ffea600e6cbe168572c0258871510 https://doi.org/10.1038/nature10251
حقوق:
OPEN
رقم الأكسشن:
edsair.doi.dedup.....108ffea600e6cbe168572c0258871510
قاعدة البيانات:
OpenAIRE
