New Results
The Multiple Sclerosis Genomic Map: Role of peripheral immune cells and resident microglia in susceptibility
International Multiple Sclerosis Genetics Consortium, NA Patsopoulos, SE Baranzini, A Santaniello, P Shoostari, C Cotsapas, G Wong, AH Beecham, T James, J Replogle, I Vlachos, C McCabe, T Pers, A Brandes, C White, B Keenan, M Cimpean, P Winn, IP Panteliadis, A Robbins, TFM Andlauer, O Zarzycki, B Dubois, A Goris, H Bach Sondergaard, F Sellebjerg, P Soelberg Sorensen, H Ullum, L Wegner Thoerner, J Saarela, I Cournu Rebeix, V Damotte, B Fontaine, L Guillot Noel, M Lathrop, S Vukusik, A Berthele, V Biberacher, D Buck, C Gasperi, C Graetz, V Grummel, B Hemmer, M Hoshi, B Knier, T Korn, CM Lill, F Luessi, M Mühlau, F Zipp, E Dardiotis, C Agliardi, A Amoroso, N Barizzone, MD Benedetti, L Bernardinelli, P Cavalla, F Clarelli, G Comi, D Cusi, F Esposito, L Ferrè, D Galimberti, C Guaschino, MA Leone, V Martinelli, L Moiola, M Salvetti, M Sorosina, D Vecchio, A Zauli, S Santoro, M Zuccalà, J Mescheriakova, C van Duijn, SD Bos, EG Celius, A Spurkland, M Comabella, X Montalban, L Alfredsson, I Bomfim, D Gomez-Cabrero, J Hillert, M Jagodic, M Lindén, F Piehl, I Jelčić, R Martin, M Sospedra, A Baker, M Ban, C Hawkins, P Hysi, S Kalra, F Karpe, J Khadake, G Lachance, P Molyneux, M Neville, J Thorpe, E Bradshaw, SJ Caillier, P Calabresi, BAC Cree, A Cross, M Davis, PWI de Bakker, S Delgado, M Dembele, K Edwards, K Fitzgerald, IY Frohlich, PA Gourraud, JL Haines, H Hakonarson, D Kimbrough, N Isobe, I Konidari, E Lathi, MH Lee, T Li, D An, A Zimmer, A Lo, L Madireddy, CP Manrique, M Mitrovic, M Olah, E Patrick, MA Pericak-Vance, L Piccio, C Schaefer, H Weiner, K Lage, A Compston, D Hafler, HF Harbo, SL Hauser, G Stewart, S D’Alfonso, G Hadjigeorgiou, B Taylor, LF Barcellos, D Booth, R Hintzen, I Kockum, F Martinelli-Boneschi, JL McCauley, JR Oksenberg, A Oturai, S Sawcer, AJ Ivinson, T Olsson, PL De Jager, Murray Barclay, Laurent Peyrin-Biroulet, Mathias Chamaillard, Jean-Frederick Colombe, Mario Cottone, Anthony Croft, Renata D’Incà, Jonas Halfvarson, Katherine Hanigan, Paul Henderson, Jean-Pierre Hugot, Amir Karban, Nicholas A Kennedy, Mohammed Azam Khan, Marc Lémann, Arie Levine, Dunecan Massey, Monica Milla, Grant W Montgomery, Sok Meng Evelyn Ng, Ioannis Oikonomou, Harald Peeters, Deborah D. Proctor, Jean-Francois Rahier, Rebecca Roberts, Paul Rutgeerts, Frank Seibold, Laura Stronati, Kirstin M Taylor, Leif Törkvist, Kullak Ublick, Johan Van Limbergen, Andre Van Gossum, Morten H. Vatn, Hu Zhang, Wei Zhang, Australia and New Zealand IBDGC, Belgium Genetic Consortium, Initiative on Crohn and Colitis, NIDDK IBDGC, United Kingdom IBDGC, Wellcome Trust Case Control Consortium
doi: https://doi.org/10.1101/143933
Systems Biology and Computer Science Program, Ann Romney Center for Neurological Diseases, Department of Neurology, Brigham & Women's Hospital, Boston, 02115 MA, USA
- For correspondence: pld2115@cumc.columbia.edu
NA Patsopoulos
Systems Biology and Computer Science Program, Ann Romney Center for Neurological Diseases, Department of Neurology, Brigham & Women's Hospital, Boston, 02115 MA, USADivision of Genetics, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USAHarvard Medical School, Boston, MA 02115, USABroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA
SE Baranzini
Department of Neurology, University of California at San Francisco, Sandler Neurosciences Center, 675 Nelson Rising Lane, San Francisco, CA 94158, USA
A Santaniello
Department of Neurology, University of California at San Francisco, Sandler Neurosciences Center, 675 Nelson Rising Lane, San Francisco, CA 94158, USA
P Shoostari
Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USADepartment of Neurology, Yale University School of Medicine, New Haven, CT 06520, USADepartment of Genetics, Yale School of Medicine, New Haven, CT 06520, USA
C Cotsapas
Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USADepartment of Neurology, Yale University School of Medicine, New Haven, CT 06520, USADepartment of Genetics, Yale School of Medicine, New Haven, CT 06520, USA
G Wong
Systems Biology and Computer Science Program, Ann Romney Center for Neurological Diseases, Department of Neurology, Brigham & Women's Hospital, Boston, 02115 MA, USAHarvard Medical School, Boston, MA 02115, USA
AH Beecham
John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA
T James
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
J Replogle
Center for Translational & Computational Neuroimmunology, Multiple Sclerosis Center, Department of Neurology, Columbia University Medical Center, New York, NY, USA
I Vlachos
Systems Biology and Computer Science Program, Ann Romney Center for Neurological Diseases, Department of Neurology, Brigham & Women's Hospital, Boston, 02115 MA, USAHarvard Medical School, Boston, MA 02115, USABroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA
C McCabe
Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA
T Pers
The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2100, Denmark
A Brandes
Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA
C White
Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USACenter for Translational & Computational Neuroimmunology, Multiple Sclerosis Center, Department of Neurology, Columbia University Medical Center, New York, NY, USA
B Keenan
Center for Translational & Computational Neuroimmunology, Multiple Sclerosis Center, Department of Neurology, Columbia University Medical Center, New York, NY, USA
M Cimpean
Center for Translational & Computational Neuroimmunology, Multiple Sclerosis Center, Department of Neurology, Columbia University Medical Center, New York, NY, USA
P Winn
Center for Translational & Computational Neuroimmunology, Multiple Sclerosis Center, Department of Neurology, Columbia University Medical Center, New York, NY, USA
IP Panteliadis
Systems Biology and Computer Science Program, Ann Romney Center for Neurological Diseases, Department of Neurology, Brigham & Women's Hospital, Boston, 02115 MA, USABroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA
A Robbins
Center for Translational & Computational Neuroimmunology, Multiple Sclerosis Center, Department of Neurology, Columbia University Medical Center, New York, NY, USA
TFM Andlauer
Max Planck Institute of Psychiatry, 80804 Munich, GermanyMunich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany
O Zarzycki
Systems Biology and Computer Science Program, Ann Romney Center for Neurological Diseases, Department of Neurology, Brigham & Women's Hospital, Boston, 02115 MA, USABroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA
B Dubois
Laboratory for Neuroimmunology, Section of Experimental Neurology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium
A Goris
Laboratory for Neuroimmunology, Section of Experimental Neurology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium
H Bach Sondergaard
Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Section 6311, 2100 Copenhagen, Denmark
F Sellebjerg
Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Section 6311, 2100 Copenhagen, Denmark
P Soelberg Sorensen
Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Section 6311, 2100 Copenhagen, Denmark
H Ullum
Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Section 2082, 2100 Copenhagen, Denmark
L Wegner Thoerner
Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Section 2082, 2100 Copenhagen, Denmark
J Saarela
Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
I Cournu Rebeix
INSERM UMR S 975 CRICM, UPMC, Departement de Neurologie Pitie-Salpetriere, AP-HP 75013 PARIS, France
V Damotte
INSERM UMR S 975 CRICM, UPMC, Departement de Neurologie Pitie-Salpetriere, AP-HP 75013 PARIS, France
B Fontaine
INSERM UMR S 975 CRICM, UPMC, Departement de Neurologie Pitie-Salpetriere, AP-HP 75013 PARIS, France
L Guillot Noel
INSERM UMR S 975 CRICM, UPMC, Departement de Neurologie Pitie-Salpetriere, AP-HP 75013 PARIS, France
M Lathrop
Commissariat à l′Energie Atomique, Institut Genomique, Centre National de Génotypage, Evry, FranceFondation Jean Dausset - Centre d'Etude du Polymorphisme Humain, Paris, FranceMcGill University and Genome Quebec Innovation Center, Montreal, Canada
S Vukusik
INSERM UMR S 975 CRICM, UPMC, Departement de Neurologie Pitie-Salpetriere, AP-HP 75013 PARIS, France
A Berthele
Department of Neurology, Klinikum rechts der Isar, Technische Universitat Munchen, Ismaninger Strasse 22, 81675 Munich, Germany
V Biberacher
Department of Neurology, Klinikum rechts der Isar, Technische Universitat Munchen, Ismaninger Strasse 22, 81675 Munich, Germany
D Buck
Department of Neurology, Klinikum rechts der Isar, Technische Universitat Munchen, Ismaninger Strasse 22, 81675 Munich, Germany
C Gasperi
Department of Neurology, Klinikum rechts der Isar, Technische Universitat Munchen, Ismaninger Strasse 22, 81675 Munich, Germany
C Graetz
Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University-Medical Center, Mainz, Germany
V Grummel
Department of Neurology, Klinikum rechts der Isar, Technische Universitat Munchen, Ismaninger Strasse 22, 81675 Munich, Germany
B Hemmer
Department of Neurology, Klinikum rechts der Isar, Technische Universitat Munchen, Ismaninger Strasse 22, 81675 Munich, GermanyMunich Cluster for Systems Neurology (SyNergy), Munich, GermanyGerman competence network for multiple sclerosis
M Hoshi
Department of Neurology, Klinikum rechts der Isar, Technische Universitat Munchen, Ismaninger Strasse 22, 81675 Munich, Germany
B Knier
Department of Neurology, Klinikum rechts der Isar, Technische Universitat Munchen, Ismaninger Strasse 22, 81675 Munich, Germany
T Korn
Department of Neurology, Klinikum rechts der Isar, Technische Universitat Munchen, Ismaninger Strasse 22, 81675 Munich, GermanyMunich Cluster for Systems Neurology (SyNergy), Munich, GermanyGerman competence network for multiple sclerosis
CM Lill
Department of Neurology, Focus Program Translational Neuroscience (FTN), and Immunology (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, GermanyGenetic and Molecular Epidemiology Group, Institute of Neurogenetics, University of Luebeck, Luebeck, Germany
F Luessi
Department of Neurology, Focus Program Translational Neuroscience (FTN), and Immunology (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
M Mühlau
Department of Neurology, Klinikum rechts der Isar, Technische Universitat Munchen, Ismaninger Strasse 22, 81675 Munich, Germany
F Zipp
Department of Neurology, Focus Program Translational Neuroscience (FTN), and Immunology (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
E Dardiotis
Neurology Dpt, Neurogenetics Lab, University Hospital of Larissa, Greece
C Agliardi
Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi Foundation ONLUS, IRCCS S. Maria Nascente, Milan, Italy
A Amoroso
Department of Medical Sciences, Torino University, Turin, Italy
N Barizzone
Department of Health Sciences and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Novara, Italy
MD Benedetti
Centro Regionale Sclerosi Multipla, Neurologia B, AOUI Verona, ItalyFondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Italy
L Bernardinelli
Medical Research Council Biostatistics Unit, Robinson Way, Cambridge CB2 0SR, UK
P Cavalla
MS Center, Department of Neuroscience, A.O. Città della Salute e della Scienza di Torino & University of Turin, Torino, Italy
F Clarelli
Laboratory of Human Genetics of Neurological complex disorder, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy
G Comi
Laboratory of Human Genetics of Neurological complex disorder, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, ItalyDepartment of Biomedical Sciences for Health, University of Milan, Milan, Italy
D Cusi
University of Milan, Department of Health Sciences, San Paolo Hospital and Filarete Foundation, viale Ortles 22/4, 20139 Milan, Italy
F Esposito
Laboratory of Human Genetics of Neurological complex disorder, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, ItalyDepartment of Neurology, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy
L Ferrè
Department of Neurology, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy
D Galimberti
Neurology Unit, Dept. of Pathophysiology and Transplantation, University of Milan
C Guaschino
Laboratory of Human Genetics of Neurological complex disorder, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, ItalyDepartment of Neurology, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy
MA Leone
Department of Neurology, Ospedale Maggiore, Novara, Italy
V Martinelli
Department of Neurology, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy
L Moiola
Department of Neurology, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy
M Salvetti
Center for Experimental Neurological Therapy (CENTERS), Neurology and Department of Neurosciences, Mental Health and Sensory Organs, Università La Sapienza, Roma, Italy
M Sorosina
Laboratory of Human Genetics of Neurological complex disorder, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy
D Vecchio
Department of Neurology, Ospedale Maggiore, Novara, Italy
A Zauli
Laboratory of Human Genetics of Neurological complex disorder, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy
S Santoro
Laboratory of Human Genetics of Neurological complex disorder, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy
M Zuccalà
Department of Health Sciences and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Novara, Italy
J Mescheriakova
Department of Neurology, Erasmus MC, Rotterdam, Netherlands
C van Duijn
Department of Neurology, Erasmus MC, Rotterdam, Netherlands
SD Bos
Department of Neurology, Institute of Clinical Medicine, University of Oslo, Norway
EG Celius
Department of Neurology, Oslo University Hospital, Oslo, Norway
A Spurkland
Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
M Comabella
Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d’Hebron (VHIR), Hospital Universitari Vall d’Hebron, Spain
X Montalban
Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d’Hebron (VHIR), Hospital Universitari Vall d’Hebron, Spain
L Alfredsson
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
I Bomfim
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
D Gomez-Cabrero
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
J Hillert
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
M Jagodic
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
M Lindén
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
F Piehl
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
I Jelčić
Neuroimmunology and MS Research (nims), Neurology Clinic, University Hospital Zurich, Frauenklinikstrasse 26, 8091 Zurich, SwitzerlandDepartment of Neuroimmunology and MS Research, Neurology Clinic, University Hospital Zürich, Frauenklinikstrasse 26, 8091 Zürich, Switzerland
R Martin
Neuroimmunology and MS Research (nims), Neurology Clinic, University Hospital Zurich, Frauenklinikstrasse 26, 8091 Zurich, SwitzerlandDepartment of Neuroimmunology and MS Research, Neurology Clinic, University Hospital Zürich, Frauenklinikstrasse 26, 8091 Zürich, Switzerland
M Sospedra
Neuroimmunology and MS Research (nims), Neurology Clinic, University Hospital Zurich, Frauenklinikstrasse 26, 8091 Zurich, SwitzerlandDepartment of Neuroimmunology and MS Research, Neurology Clinic, University Hospital Zürich, Frauenklinikstrasse 26, 8091 Zürich, Switzerland
A Baker
University of Cambridge, Department of Clinical Neurosciences, Addenbrooke's Hospital, BOX 165, Hills Road, Cambridge CB2 0QQ, UK
M Ban
University of Cambridge, Department of Clinical Neurosciences, Addenbrooke's Hospital, BOX 165, Hills Road, Cambridge CB2 0QQ, UK
C Hawkins
Keele University Medical School, University Hospital of North Staffordshire, Stoke-on-Trent ST4 7NY, UK
P Hysi
Department of Twin Research and Genetic Epidemiology, King’s College London, London, SE1 7EH, UK
S Kalra
Keele University Medical School, University Hospital of North Staffordshire, Stoke-on-Trent ST4 7NY, UK
F Karpe
Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 7LE, UK
J Khadake
NIHR BioResource, Box 299,University of Cambridge and Cambridge University Hospitals NHS Foundation Trust Hills Road, Cambridge CB2 0QQ, UK
G Lachance
Department of Twin Research and Genetic Epidemiology, King’s College London, London, SE1 7EH, UK
P Molyneux
University of Cambridge, Department of Clinical Neurosciences, Addenbrooke's Hospital, BOX 165, Hills Road, Cambridge CB2 0QQ, UK
M Neville
Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 7LE, UK
J Thorpe
Department of Neurology, Peterborough City Hospital, Edith Cavell Campus, Bretton Gate, Peterborough PE3 9GZ, UK
E Bradshaw
Center for Translational & Computational Neuroimmunology, Multiple Sclerosis Center, Department of Neurology, Columbia University Medical Center, New York, NY, USA
SJ Caillier
Department of Neurology, University of California at San Francisco, Sandler Neurosciences Center, 675 Nelson Rising Lane, San Francisco, CA 94158, USA
P Calabresi
Department of Neurology, Johns Hopkins University School of medicine, Baltimore MD
BAC Cree
Department of Neurology, University of California at San Francisco, Sandler Neurosciences Center, 675 Nelson Rising Lane, San Francisco, CA 94158, USA
A Cross
Multiple sclerosis center, Department of neurology, School of medicine, Washington University St Louis, St Louis MO
M Davis
Center for Human Genetics Research, Vanderbilt University Medical Center, 525 Light Hall, 2215 Garland Avenue, Nashville, TN 37232, USA
PWI de Bakker
Division of Genetics, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USAHarvard Medical School, Boston, MA 02115, USABroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA
S Delgado
Multiple Sclerosis Division, Department of Neurology, University of Miami, Miller School of Medicine, Miami, FL 33136, USA
M Dembele
Department of Neurology, Johns Hopkins University School of medicine, Baltimore MD
K Edwards
MS Center of Northeastern NY 1205 Troy Schenectady Rd, Latham, NY 12110
K Fitzgerald
Department of Neurology, Johns Hopkins University School of medicine, Baltimore MD
IY Frohlich
Center for Translational & Computational Neuroimmunology, Multiple Sclerosis Center, Department of Neurology, Columbia University Medical Center, New York, NY, USA
PA Gourraud
Department of Neurology, University of California at San Francisco, Sandler Neurosciences Center, 675 Nelson Rising Lane, San Francisco, CA 94158, USAITUN - CRTI - UMR Inserm 1064 - Nantes University and Hopsitals, France
JL Haines
Population & Quantitative Health Sciences, Department of Epidemiology and Biostatistics, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4945 USA
H Hakonarson
Center for Applied Genomics, The Children's Hospital of Philadelphia, 3615 Civic Center Blvd., Philadelphia, PA 19104, USADepartment of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia PA, USA
D Kimbrough
Department of Neurology, Brigham & Women's Hospital, Boston, 02115 MA, USA
N Isobe
Department of Neurology, University of California at San Francisco, Sandler Neurosciences Center, 675 Nelson Rising Lane, San Francisco, CA 94158, USA
I Konidari
John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA
E Lathi
The Elliot Lewis Center, 110 Cedar St, Wellesley MA, 02481, USA
MH Lee
Center for Translational & Computational Neuroimmunology, Multiple Sclerosis Center, Department of Neurology, Columbia University Medical Center, New York, NY, USA
T Li
Broad Institute of Harvard University and MIT, Cambridge, 02142 MA, USA
D An
Broad Institute of Harvard University and MIT, Cambridge, 02142 MA, USA
A Zimmer
Broad Institute of Harvard University and MIT, Cambridge, 02142 MA, USA
A Lo
Mt. Sinai Rehab Hospital, Mandell MS Center, Hartford, CT 06112, USA
L Madireddy
Department of Neurology, University of California at San Francisco, Sandler Neurosciences Center, 675 Nelson Rising Lane, San Francisco, CA 94158, USA
CP Manrique
John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA
M Mitrovic
Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USADepartment of Neurology, Yale University School of Medicine, New Haven, CT 06520, USADepartment of Genetics, Yale School of Medicine, New Haven, CT 06520, USA
M Olah
Center for Translational & Computational Neuroimmunology, Multiple Sclerosis Center, Department of Neurology, Columbia University Medical Center, New York, NY, USA
E Patrick
Center for Translational & Computational Neuroimmunology, Multiple Sclerosis Center, Department of Neurology, Columbia University Medical Center, New York, NY, USA
MA Pericak-Vance
John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA
L Piccio
Multiple sclerosis center, Department of neurology, School of medicine, Washington University St Louis, St Louis MO
C Schaefer
Kaiser Permanente Division of Research, Oakland, CA, USA
H Weiner
Ann Romney Center for Neurological Diseases, Department of Neurology, Brigham & Women's Hospital, Boston, 02115 MA, USA
K Lage
Broad Institute of Harvard University and MIT, Cambridge, 02142 MA, USA
A Compston
University of Cambridge, Department of Clinical Neurosciences, Addenbrooke's Hospital, BOX 165, Hills Road, Cambridge CB2 0QQ, UK
D Hafler
Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USADepartments of Neurology and Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
HF Harbo
Department of Neurology, Institute of Clinical Medicine, University of Oslo, NorwayDepartment of Neurology, Oslo University Hospital, Oslo, Norway
SL Hauser
Department of Neurology, University of California at San Francisco, Sandler Neurosciences Center, 675 Nelson Rising Lane, San Francisco, CA 94158, USA
G Stewart
Westmead Millennium Institute, University of Sydney, New South Wales, Australia
S D’Alfonso
Department of Health Sciences and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Novara, Italy
G Hadjigeorgiou
Neurology Dpt, Neurogenetics Lab, University Hospital of Larissa, Greece
B Taylor
Menzies Research Institute Tasmania, University of Tasmania, Australia
LF Barcellos
UC Berkeley School of Public Health and Center for Computational Biology, USA
D Booth
Westmead Millennium Institute, University of Sydney, New South Wales, Australia
R Hintzen
Department of Neurology and Department of Immunology, Erasmus MC, Rotterdam, Netherlands
I Kockum
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
F Martinelli-Boneschi
Laboratory of Human Genetics of Neurological complex disorder, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, ItalyDepartment of Biomedical Sciences for Health, University of Milan, Milan, Italy
JL McCauley
John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA
JR Oksenberg
Department of Neurology, University of California at San Francisco, Sandler Neurosciences Center, 675 Nelson Rising Lane, San Francisco, CA 94158, USA
A Oturai
Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Section 6311, 2100 Copenhagen, Denmark
S Sawcer
University of Cambridge, Department of Clinical Neurosciences, Addenbrooke's Hospital, BOX 165, Hills Road, Cambridge CB2 0QQ, UK
AJ Ivinson
BWH Institute for the Neurosciences and the Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham & Women's Hospital, Boston, 02115 MA, USA
T Olsson
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
PL De Jager
Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USACenter for Translational & Computational Neuroimmunology, Multiple Sclerosis Center, Department of Neurology, Columbia University Medical Center, New York, NY, USA
Murray Barclay
Department of Medicine, University of Otago, Christchurch, New Zealand
Laurent Peyrin-Biroulet
Gastroenterology Unit, INSERM U954, Nancy University and Hospital, France
Mathias Chamaillard
INSERM, U1019, Lille, France
Jean-Frederick Colombe
Univ Lille Nord de France, CHU Lille and Lille-2 University, Gastroenterology Unit, France
Mario Cottone
Division of Internal Medicine, Villa Sofia-V. Cervello Hospital, University of Palermo, Palermo, Italy
Anthony Croft
Inflammatory Bowel Diseases, Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, Australia
Renata D’Incà
Department of Surgical and Gastroenterological Sciences, University of Padua, Padua, Italy
Jonas Halfvarson
Department of Medicine, Örebro University Hospital, Örebro, SwedenSchool of Health and Medical Sciences, Örebro University, Örebro, Sweden
Katherine Hanigan
Inflammatory Bowel Diseases, Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, Australia
Paul Henderson
Royal Hospital for Sick Children, Paediatric Gastroenterology and Nutrition, Edinburgh, UKChild Life and Health, University of Edinburgh, Edinburgh, UK
Jean-Pierre Hugot
INSERM U843, Paris, FranceUniv-Paris Diderot Sorbonne Paris-Cité, Paris France
Amir Karban
Department of Gastroenterology, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
Nicholas A Kennedy
Gastrointestinal Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
Mohammed Azam Khan
Genetic Medicine, MAHSC, University of Manchester, Manchester, UK
Marc Lémann
Université Paris Diderot, GETAID group, Paris, France
Arie Levine
Pediatric Gastroenterology Unit, Wolfson Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Dunecan Massey
Inflammatory Bowel Disease Research Group, Addenbrooke’s Hospital, University of Cambridge, Cambridge, UK
Monica Milla
Azienda Ospedaliero Universitaria (AOU) Careggi, Unit of Gastroenterology SOD2, Florence, Italy
Grant W Montgomery
Molecular Epidemiology, Queensland Institute of Medical Research, Brisbane, Australia
Sok Meng Evelyn Ng
Department of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, USA
Ioannis Oikonomou
Department of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, USA
Harald Peeters
Dept Gastroenterology - University hospital Gent - De Pintelaan - 9000 Gent Belgium
Deborah D. Proctor
Department of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, USA
Jean-Francois Rahier
Dept Gastroenterology - UCL Mont Godinne Belgium
Rebecca Roberts
Gastroenterology Unit, INSERM U954, Nancy University and Hospital, France
Paul Rutgeerts
Division of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium
Frank Seibold
University of Bern, Division of Gastroenterology, Inselspital, Bern
Laura Stronati
INSERM, U1019, Lille, France
Kirstin M Taylor
Neurology Dpt, Neurogenetics Lab, University Hospital of Larissa, Greece
Leif Törkvist
Department of Medicine, University of Otago, Christchurch, New Zealand
Kullak Ublick
Gastroenterology Unit, INSERM U954, Nancy University and Hospital, France
Johan Van Limbergen
INSERM, U1019, Lille, France
Andre Van Gossum
Univ Lille Nord de France, CHU Lille and Lille-2 University, Gastroenterology Unit, France
Morten H. Vatn
Division of Internal Medicine, Villa Sofia-V. Cervello Hospital, University of Palermo, Palermo, Italy
Hu Zhang
Azienda Ospedaliero Universitaria (AOU) Careggi, Unit of Gastroenterology SOD2, Florence, Italy
Wei Zhang
Department of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, USA
- For correspondence: pld2115@cumc.columbia.edu
Abstract:
We assembled and analyzed genetic data of 47,351 multiple sclerosis (MS) subjects and 68,284 control subjects and establish a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 independent associations within the extended MHC. We used an ensemble of methods to prioritize up to 551 potentially associated MS susceptibility genes, that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we do find enrichment for MS genes in these brain - resident immune cells. Thus, while MS is most likely initially triggered by perturbation of peripheral immune responses the functional responses of microglia and other brain cells are also altered and may have a role in targeting an autoimmune process to the central nervous system.
One Sentence Summary: We report a detailed genetic and genomic map of multiple sclerosis, and describe the role of putatively affected genes in the peripheral immune system and brain resident microglia.
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
Posted July 13, 2017.
The Multiple Sclerosis Genomic Map: Role of peripheral immune cells and resident microglia in susceptibility
International Multiple Sclerosis Genetics Consortium, NA Patsopoulos, SE Baranzini, A Santaniello, P Shoostari, C Cotsapas, G Wong, AH Beecham, T James, J Replogle, I Vlachos, C McCabe, T Pers, A Brandes, C White, B Keenan, M Cimpean, P Winn, IP Panteliadis, A Robbins, TFM Andlauer, O Zarzycki, B Dubois, A Goris, H Bach Sondergaard, F Sellebjerg, P Soelberg Sorensen, H Ullum, L Wegner Thoerner, J Saarela, I Cournu Rebeix, V Damotte, B Fontaine, L Guillot Noel, M Lathrop, S Vukusik, A Berthele, V Biberacher, D Buck, C Gasperi, C Graetz, V Grummel, B Hemmer, M Hoshi, B Knier, T Korn, CM Lill, F Luessi, M Mühlau, F Zipp, E Dardiotis, C Agliardi, A Amoroso, N Barizzone, MD Benedetti, L Bernardinelli, P Cavalla, F Clarelli, G Comi, D Cusi, F Esposito, L Ferrè, D Galimberti, C Guaschino, MA Leone, V Martinelli, L Moiola, M Salvetti, M Sorosina, D Vecchio, A Zauli, S Santoro, M Zuccalà, J Mescheriakova, C van Duijn, SD Bos, EG Celius, A Spurkland, M Comabella, X Montalban, L Alfredsson, I Bomfim, D Gomez-Cabrero, J Hillert, M Jagodic, M Lindén, F Piehl, I Jelčić, R Martin, M Sospedra, A Baker, M Ban, C Hawkins, P Hysi, S Kalra, F Karpe, J Khadake, G Lachance, P Molyneux, M Neville, J Thorpe, E Bradshaw, SJ Caillier, P Calabresi, BAC Cree, A Cross, M Davis, PWI de Bakker, S Delgado, M Dembele, K Edwards, K Fitzgerald, IY Frohlich, PA Gourraud, JL Haines, H Hakonarson, D Kimbrough, N Isobe, I Konidari, E Lathi, MH Lee, T Li, D An, A Zimmer, A Lo, L Madireddy, CP Manrique, M Mitrovic, M Olah, E Patrick, MA Pericak-Vance, L Piccio, C Schaefer, H Weiner, K Lage, A Compston, D Hafler, HF Harbo, SL Hauser, G Stewart, S D’Alfonso, G Hadjigeorgiou, B Taylor, LF Barcellos, D Booth, R Hintzen, I Kockum, F Martinelli-Boneschi, JL McCauley, JR Oksenberg, A Oturai, S Sawcer, AJ Ivinson, T Olsson, PL De Jager, Murray Barclay, Laurent Peyrin-Biroulet, Mathias Chamaillard, Jean-Frederick Colombe, Mario Cottone, Anthony Croft, Renata D’Incà, Jonas Halfvarson, Katherine Hanigan, Paul Henderson, Jean-Pierre Hugot, Amir Karban, Nicholas A Kennedy, Mohammed Azam Khan, Marc Lémann, Arie Levine, Dunecan Massey, Monica Milla, Grant W Montgomery, Sok Meng Evelyn Ng, Ioannis Oikonomou, Harald Peeters, Deborah D. Proctor, Jean-Francois Rahier, Rebecca Roberts, Paul Rutgeerts, Frank Seibold, Laura Stronati, Kirstin M Taylor, Leif Törkvist, Kullak Ublick, Johan Van Limbergen, Andre Van Gossum, Morten H. Vatn, Hu Zhang, Wei Zhang, Australia and New Zealand IBDGC, Belgium Genetic Consortium, Initiative on Crohn and Colitis, NIDDK IBDGC, United Kingdom IBDGC, Wellcome Trust Case Control Consortium
bioRxiv 143933; doi: https://doi.org/10.1101/143933
The Multiple Sclerosis Genomic Map: Role of peripheral immune cells and resident microglia in susceptibility
International Multiple Sclerosis Genetics Consortium, NA Patsopoulos, SE Baranzini, A Santaniello, P Shoostari, C Cotsapas, G Wong, AH Beecham, T James, J Replogle, I Vlachos, C McCabe, T Pers, A Brandes, C White, B Keenan, M Cimpean, P Winn, IP Panteliadis, A Robbins, TFM Andlauer, O Zarzycki, B Dubois, A Goris, H Bach Sondergaard, F Sellebjerg, P Soelberg Sorensen, H Ullum, L Wegner Thoerner, J Saarela, I Cournu Rebeix, V Damotte, B Fontaine, L Guillot Noel, M Lathrop, S Vukusik, A Berthele, V Biberacher, D Buck, C Gasperi, C Graetz, V Grummel, B Hemmer, M Hoshi, B Knier, T Korn, CM Lill, F Luessi, M Mühlau, F Zipp, E Dardiotis, C Agliardi, A Amoroso, N Barizzone, MD Benedetti, L Bernardinelli, P Cavalla, F Clarelli, G Comi, D Cusi, F Esposito, L Ferrè, D Galimberti, C Guaschino, MA Leone, V Martinelli, L Moiola, M Salvetti, M Sorosina, D Vecchio, A Zauli, S Santoro, M Zuccalà, J Mescheriakova, C van Duijn, SD Bos, EG Celius, A Spurkland, M Comabella, X Montalban, L Alfredsson, I Bomfim, D Gomez-Cabrero, J Hillert, M Jagodic, M Lindén, F Piehl, I Jelčić, R Martin, M Sospedra, A Baker, M Ban, C Hawkins, P Hysi, S Kalra, F Karpe, J Khadake, G Lachance, P Molyneux, M Neville, J Thorpe, E Bradshaw, SJ Caillier, P Calabresi, BAC Cree, A Cross, M Davis, PWI de Bakker, S Delgado, M Dembele, K Edwards, K Fitzgerald, IY Frohlich, PA Gourraud, JL Haines, H Hakonarson, D Kimbrough, N Isobe, I Konidari, E Lathi, MH Lee, T Li, D An, A Zimmer, A Lo, L Madireddy, CP Manrique, M Mitrovic, M Olah, E Patrick, MA Pericak-Vance, L Piccio, C Schaefer, H Weiner, K Lage, A Compston, D Hafler, HF Harbo, SL Hauser, G Stewart, S D’Alfonso, G Hadjigeorgiou, B Taylor, LF Barcellos, D Booth, R Hintzen, I Kockum, F Martinelli-Boneschi, JL McCauley, JR Oksenberg, A Oturai, S Sawcer, AJ Ivinson, T Olsson, PL De Jager, Murray Barclay, Laurent Peyrin-Biroulet, Mathias Chamaillard, Jean-Frederick Colombe, Mario Cottone, Anthony Croft, Renata D’Incà, Jonas Halfvarson, Katherine Hanigan, Paul Henderson, Jean-Pierre Hugot, Amir Karban, Nicholas A Kennedy, Mohammed Azam Khan, Marc Lémann, Arie Levine, Dunecan Massey, Monica Milla, Grant W Montgomery, Sok Meng Evelyn Ng, Ioannis Oikonomou, Harald Peeters, Deborah D. Proctor, Jean-Francois Rahier, Rebecca Roberts, Paul Rutgeerts, Frank Seibold, Laura Stronati, Kirstin M Taylor, Leif Törkvist, Kullak Ublick, Johan Van Limbergen, Andre Van Gossum, Morten H. Vatn, Hu Zhang, Wei Zhang, Australia and New Zealand IBDGC, Belgium Genetic Consortium, Initiative on Crohn and Colitis, NIDDK IBDGC, United Kingdom IBDGC, Wellcome Trust Case Control Consortium
bioRxiv 143933; doi: https://doi.org/10.1101/143933
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