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46 results on '"Hauser, S.L."'

1. A second-generation genomic screen for multiple sclerosis

Author

Kenealy, S.J., Babron, M.-C., Bradford, Y., Schnetz-Boutaud, N., Haines, J.L., Rimmler, J.B., Schmidt, S., Pericak-Vance, M.A., Barcellos, L.F., Lincoln, R.R., Oksenberg, J.R., Hauser, S.L., Clanet, M., Brassat, D., Edan, G., Yaouanq, J., Semana, G., Cournu-Rebeix, I., Lyon-Caen, O., and Fontaine, B.

Subjects
Multiple sclerosis -- Research, Biological sciences
Published
2004

2. HLA-DR2 dose effect on susceptibility to multiple sclerosis and influence on disease course. (Report)

Author

Barcellos, L.F., Oksenberg, J.R., Begovich, A.B., Martin, E.R., Schmidt, S., Vittinghoff, E., Goodin, D.S., Pelletier, D., Lincoln, R.R., Bucher, P., Swerdlin, A., Pericak-Vance, M.A., Haines, J.L., and Hauser, S.L.

Subjects
Multiple sclerosis -- Physiological aspects, Multiple sclerosis -- Genetic aspects, Histocompatibility antigens -- Physiological aspects, Histocompatibility antigens -- Genetic aspects, HLA histocompatibility antigens, Biological sciences
Published
2003

3. Unusual organization of the human T-cell receptor beta-chain gene complex is linked to recombination hotspots

Author

Seboun, E., Houghton, L., Hatem, C.J., Jr., Lincoln, R., and Hauser, S.L.

Subjects
Gel electrophoresis -- Usage, Hemoglobin polymorphisms -- Research, Antigen receptors, T cell -- Research, Science and technology
Abstract

Researchers used pulsed-field gel electrophoresis to discover 2 uncommon Sfi I polymorphisms of 360 kb and 280 kb in the human T-cell antigen receptor beta-chain gene complex. The duplication of the 30-kb DNA fragment causing the 330/300 -kb insertion/deletion-related polymorphism has resulted in the 360-kb polymorphisms. A 20-kb removal from the 300-kb Sfi I allelic has caused the 280-kb polymorphism.

Published
1993

4. Cytokine accumulations in CSF of multiple sclerosis patients: frequent detection of interleukin-1 and tumor necrosis factor but not interleukin-6

Author

Hauser, S.L., Doolittle, T.H., Lincoln, R., Brown, R.H., and Dinarello, C.A.

Subjects
Cerebrospinal fluid -- Analysis, Interleukin-1 -- Physiological aspects, Interleukins -- Physiological aspects, Multiple sclerosis -- Physiological aspects, Tumor necrosis factor -- Physiological aspects, Cytokines -- Physiological aspects, Health, Psychology and mental health
Abstract

Multiple sclerosis (MS) is generally considered to be an immune disorder, but surprisingly little is known about the development of the disease. As part of the continuing effort to identify immunological parameters that may be altered in patients with MS, investigators measured levels of the cytokines interleukin-1-beta, interleukin-6, and tumor necrosis factor in cerebrospinal fluid. The quantities were compared with levels in patients with neurological diseases unrelated to multiple sclerosis. Both interleukin-1-beta and tumor necrosis factor were found to be elevated in a significant percentage of patients with MS, compared with levels in the other patients. (The levels of interleukin-6 were unremarkable). However, the cytokine levels were not elevated in all MS patients, nor were the levels uniformly lower among all patients with other neurological diseases. The elevated levels of interleukin-1 and tumor necrosis factor could not be correlated with the presence of cells in the cerebrospinal fluid. The authors interpret this as an indication that the substances are arising from the cells within the brain tissue and not from the cells floating in the cerebrospinal fluid. It is worth noting that experiments have suggested that interleukin-1-beta and tumor necrosis factor can induce astrogliosis, demyelination, fatigue, sleep, and temperature elevation. Since all of these conditions are observed in MS, it is possible to imagine that at least some of the symptoms of MS may result directly from the effects of cytokines, such as interleukin-1-beta and tumor necrosis factor. (Consumer Summary produced by Reliance Medical Information, Inc.)

Published
1990

5. Multiple sclerosis sibling pairs: clustered onset and familial predisposition

Author

Doolittle, T.H., Myers, R.H., Lehrich, J.R., Birnbaum, G., Sheremata, W., Franklin, G.M., Nelson, L.M., and Hauser, S.L.

Subjects
Multiple sclerosis -- Genetic aspects, Multiple sclerosis -- Development and progression, Health, Psychology and mental health
Abstract

To learn more regarding the familial aspects of multiple sclerosis (MS, an inflammatory disease of the nervous system), 48 pairs of siblings with MS were studied. The siblings were multiplex siblings, since more than one individual in the family had the disorder, and they had relapsing-remitting MS (R/R MS), in which the symptoms return and then disappear. Of interest were the dates of onset: onset at approximately the same age within a family argues for the importance of inherited factors in MS, whereas onset within the same few years suggests exposure to a virus (two current hypotheses regarding the origin of MS). Results from the sibling pairs were compared with results from 96 individual MS patients (the controls), matched for age and sex to the first group. All subjects underwent a medical interview and neurologic examination. Results showed that the ages at MS onset for the multiplex siblings were frequently within a five-year range (30 out of 48 pairs). This indicates that age, rather than year of onset, influences the onset of the disorder. The pairs of siblings came from 44 families; investigation of these extended families revealed that 19 families had at least one other member with MS (a rate of 0.43). The comparable rate for the matched controls was 0.20. When relatives up through the third degree were included, 22 of 1,134 family members of multiplex pairs had MS, compared with 10 of 1,215 control family members. The results support an inherited susceptibility to MS; it is likely that such susceptibility is the consequence of the action of more than one gene. (Consumer Summary produced by Reliance Medical Information, Inc.)

Published
1990

8. P61 Sustained reduction in confirmed disability progression in patients with primary progressive multiple sclerosis treated with ocrelizumab in the open-label extension period of the Phase III ORATORIO trial

Author

Wolinsky, J.S., primary, Hartung, H.P., additional, Brochet, B., additional, Montalban, X., additional, Naismith, R.T., additional, Manfrini, M., additional, Garas, M., additional, Model, F., additional, Hubeaux, S., additional, Kappos, L., additional, and Hauser, S.L., additional

Published
2019
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9. Author Correction: A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis (Nature Communications, (2019), 10, 1, (2236), 10.1038/s41467-019-09773-y)

Author

Madireddy, L. (Lohith), Patsopoulos, N.A. (Nikolaos A.), Cotsapas, C. (Chris), Bos, S.D. (Steffan), Beecham, A.H. (Ashley), McCauley, J. (John William), Kim, K. (Kicheol), Jia, X. (Xiaoming), Santaniello, A. (Adam), Caillier, S.J. (Stacy), Andlauer, T.F.M. (Till F. M.), Barcellos, L.F. (Lisa), Berge, T. (Tone), Bernardinelli, L. (Luisa), Martinelli-Boneschi, F. (Filippo), Booth, D. (David), Briggs, F. (Farren), Celius, E.G. (Elisabeth), Comabella, M. (Manuel), Comi, G. (Giancarlo), Cree, B.A.C. (Bruce A. C.), Dalfonso, S., Dedham, K. (Katrina), Duquette, P. (Pierre), Dardiotis, E. (Efthimios), Esposito, F. (Francesco), Fontaine, B. (Bertrand), Gasperi, C. (Christiane), Goris, A. (An), Dubois, B. (Bénédicte), Gourraud, P.-A. (Pierre-Antoine), Hadjigeorgiou, G.M. (Georgios M.), Haines, J.L. (Jonathan), Hawkins, C. (Clive), Hemmer`, B. (Bernhard), Hintzen, R.Q. (Rogier), Horáková, D., Isobe, N. (Noriko), Kalra, S. (Seema), Kira, J.-I. (Jun-ichi), Khalil, M. (Michael), Kockum, I. (I.), Lill, C.M. (Christina), Lincoln, M.R. (Matthew R.), Luessi, F. (Felix), Martin, R. (Roland), Oturai, A. (Annette), Palotie, A. (Aarno), Kunkle, B. (Brian), Henry, R. (Roland), Saarela, O. (Olli), Ivinson, A.J. (Adrian), Olsson, T., Taylor, B. (Bruce), Stewart, G. (Graeme), Harbo, H.F. (H.), Compston, J.E. (Juliet), Hauser, S.L. (Stephen), Hafler, D.A. (David A.), Zipp, F. (Frauke), De Jager, P., Sawcer, S.J. (Stephen), Oksenberg, J.R. (Jorge), Baranzini, S.E. (Sergio), Madireddy, L. (Lohith), Patsopoulos, N.A. (Nikolaos A.), Cotsapas, C. (Chris), Bos, S.D. (Steffan), Beecham, A.H. (Ashley), McCauley, J. (John William), Kim, K. (Kicheol), Jia, X. (Xiaoming), Santaniello, A. (Adam), Caillier, S.J. (Stacy), Andlauer, T.F.M. (Till F. M.), Barcellos, L.F. (Lisa), Berge, T. (Tone), Bernardinelli, L. (Luisa), Martinelli-Boneschi, F. (Filippo), Booth, D. (David), Briggs, F. (Farren), Celius, E.G. (Elisabeth), Comabella, M. (Manuel), Comi, G. (Giancarlo), Cree, B.A.C. (Bruce A. C.), Dalfonso, S., Dedham, K. (Katrina), Duquette, P. (Pierre), Dardiotis, E. (Efthimios), Esposito, F. (Francesco), Fontaine, B. (Bertrand), Gasperi, C. (Christiane), Goris, A. (An), Dubois, B. (Bénédicte), Gourraud, P.-A. (Pierre-Antoine), Hadjigeorgiou, G.M. (Georgios M.), Haines, J.L. (Jonathan), Hawkins, C. (Clive), Hemmer`, B. (Bernhard), Hintzen, R.Q. (Rogier), Horáková, D., Isobe, N. (Noriko), Kalra, S. (Seema), Kira, J.-I. (Jun-ichi), Khalil, M. (Michael), Kockum, I. (I.), Lill, C.M. (Christina), Lincoln, M.R. (Matthew R.), Luessi, F. (Felix), Martin, R. (Roland), Oturai, A. (Annette), Palotie, A. (Aarno), Kunkle, B. (Brian), Henry, R. (Roland), Saarela, O. (Olli), Ivinson, A.J. (Adrian), Olsson, T., Taylor, B. (Bruce), Stewart, G. (Graeme), Harbo, H.F. (H.), Compston, J.E. (Juliet), Hauser, S.L. (Stephen), Hafler, D.A. (David A.), Zipp, F. (Frauke), De Jager, P., Sawcer, S.J. (Stephen), Oksenberg, J.R. (Jorge), and Baranzini, S.E. (Sergio)

Abstract

The original version of this Article contained an error in the spelling of the author Nikolaos A. Patsopoulos, which was incorrectly given as Niklaos A. Patsopoulos, and author Efthimios Dardiotis, which was incorrectly given as Dardiotis Efthimios. This has now been corrected in both the PDF and HTML versions of the Article.

Published
2019
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13. Sustained Reduction in Confirmed Disability Progression in Patients with Primary Progressive Multiple Sclerosis Treated with Ocrelizumab in the Open-label Extension Period of the Phase III ORATORIO trial

Author

Hauser, S.L., primary, Wolinsky, J.S., additional, Brochet, B., additional, Montalban, X., additional, Naismith, R.T., additional, Manfrini, M., additional, Garas, M., additional, Villoslada, P., additional, Model, F., additional, Hubeaux, S., additional, and Kappos, L., additional

Published
2018
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14. Long-term Reduction in Brain MRI Disease Activity and Atrophy after 5 years of Ocrelizumab Treatment in Patients with Relapsing Multiple Sclerosis

Author

Arnold, D.L., primary, Kappos, L., additional, Hauser, S.L., additional, Montalban, X., additional, Traboulsee, A., additional, Wolinsky, J.S., additional, Manfrini, M., additional, Levesque, V., additional, Villoslada, P., additional, Belachew, S., additional, Model, F., additional, Hubeaux, S., additional, and Bar-Or, A., additional

Published
2018
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15. P 1 Effect of ocrelizumab on magnetic resonance imaging markers of neurodegeneration in patients with relapsing multiple sclerosis – analysis of the phase III, double-blind, double-dummy, interferon beta-1a- controlled OPERA I and OPERA II studies

Author

Ziemssen, T., primary, Arnold, D.L., additional, Bar-Or, A., additional, Comi, G., additional, Hartung, H.P., additional, Hauser, S.L., additional, Kappos, L., additional, Lublin, F., additional, Selmaj, K., additional, Traboulsee, A., additional, Masterman, D., additional, Chin, P., additional, Garren, H., additional, and Wolinsky, J.S., additional

Published
2017
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16. P 2 Effect of ocrelizumab on humoral immunity markers in the phase iii, double-blind, double-dummy, IFNβ-1a–controlled OPERA I and OPERA II studies

Author

Ziemssen, T., primary, Bar-Or, A., additional, Arnold, D.L., additional, Comi, G., additional, Hartung, H.P., additional, Hauser, S.L., additional, Lublin, F., additional, Selmaj, K., additional, Traboulsee, A., additional, Chin, P., additional, Fontoura, P., additional, Garren, H., additional, Masterman, D., additional, and Kappos, L., additional

Published
2017
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17. Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models

Author

Cekanaviciute, E. (Egle), Yoo, B.B. (Bryan B.), Runia, T.F. (Tessel), Debelius, J.W. (Justine W.), Singh, S. (Sneha), Nelson, C.A. (Charlotte A.), Kanner, R. (Rachel), Bencosme, Y. (Yadira), Lee, Y.K. (Yun Kyung), Hauser, S.L. (Stephen), Crabtree-Hartman, E. (Elizabeth), Sand, I.K. (Ilana Katz), Gacias, M. (Mar), Zhu, Y. (Yungjiao), Casaccia, P. (Patrizia), Cree, B.A.C. (Bruce A. C.), Knight, R. (Rob), Mazmanian, S.K. (Sarkis K.), Baranzini, S.E. (Sergio), Cekanaviciute, E. (Egle), Yoo, B.B. (Bryan B.), Runia, T.F. (Tessel), Debelius, J.W. (Justine W.), Singh, S. (Sneha), Nelson, C.A. (Charlotte A.), Kanner, R. (Rachel), Bencosme, Y. (Yadira), Lee, Y.K. (Yun Kyung), Hauser, S.L. (Stephen), Crabtree-Hartman, E. (Elizabeth), Sand, I.K. (Ilana Katz), Gacias, M. (Mar), Zhu, Y. (Yungjiao), Casaccia, P. (Patrizia), Cree, B.A.C. (Bruce A. C.), Knight, R. (Rob), Mazmanian, S.K. (Sarkis K.), and Baranzini, S.E. (Sergio)

Abstract

The gut microbiota regulates T cell functions throughout the body. We hypothesized that intestinal bacteria impact the pathogenesis of multiple sclerosis (MS), an autoimmune disorder of the CNS and thus analyzed the microbiomes of 71 MS patients not undergoing treatment and 71 healthy controls. Although no major shifts in microbial community structure were found, we identified specific bacterial taxa that were significantly associated with MS. Akkermansia muciniphila and Acinetobacter calcoaceticus, both increased in MS patients, induced proinflammatory responses in human peripheral blood mononuclear cells and in monocolonized mice. In contrast, Parabacteroides distasonis, which was reduced in MS patients, stimulated antiinflammatory IL-10–expressing human CD4+CD25+ T cells and IL-10+FoxP3+ Tregs in mice. Finally, microbiota transplants from MS patients into germ-free mice resulted in more severe symptoms of experimental autoimmune encephalomyelitis and reduced proportions of IL-10+ Tregs compared with mice “humanized” with microbiota from healthy controls. This study identifies specific human gut bacteria that regulate adaptive autoimmune responses, suggesting therapeutic targeting of the microbiota as a treatment for MS.

Published
2017
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19. Modulation of severity in multiple sclerosis by polymorphisms in and around APOE

Author

Haines, J.L., Schmidt, S., Barcellos, L.F., deSombre, K., Lincoln, A.M., Bucher, P., Martin, E.R., Lai, E., Saunders, R.R., Vance, J.M., Oksenberg, J.R., Hauser, S.L., and Pericak-Vance, M.A.

Subjects
Human genetics -- Research, Multiple sclerosis -- Genetic aspects, Genetic polymorphisms -- Research, Chromosomes -- Research, Biological sciences
Published
2001

21. The transforming growth factor-[Beta]1 locus (TGFB1) on ch.19q13 and clinical phenotypes in familial multiple sclerosis (MS)

Author

Green, A.J., Barcellos, L.F., Rimmler, J.B., Caillier, S., Bucher, P., Lincoln, R.R., Garcia, M.E., Haines, J.L., Pericak-Vance, M.A., Hauser, S.L., and Oksenberg, J.R.

Subjects
Genetic research -- Analysis, Human genetics -- Research, Multiple sclerosis -- Genetic aspects, Growth factors -- Genetic aspects, Phenotype -- Research, Biological sciences
Published
2000

24. 2D phase sensitive inversion recovery imaging to measure in-vivo spinal cord gray and white matter areas in clinically feasible acquisition times

Author

Papinutto, N., Schlaeger, R., Panara, V., Caverzasi, E., Ahn, S., Johnson, K.J., Zhu, A.H., Stern, W.A., Laub, G., Hauser, S.L., and Henry, R.G.

Subjects
Adult, Male, Time Factors, Reproducibility of Results, Middle Aged, Signal-To-Noise Ratio, Magnetic Resonance Imaging, White Matter, Article, Healthy Volunteers, Cohort Studies, Cross-Sectional Studies, Spinal Cord, Reference Values, Image Processing, Computer-Assisted, Humans, Female, Whole Body Imaging, Gray Matter, Nervous System Diseases, Aged
Abstract

To present and assess a procedure for measurement of spinal cord total cross-sectional areas (TCA) and gray matter (GM) areas based on phase-sensitive inversion recovery imaging (PSIR). In vivo assessment of spinal cord GM and white matter (WM) could become pivotal to study various neurological diseases, but it is challenging because of insufficient GM/WM contrast provided by conventional magnetic resonance imaging (MRI).We acquired 2D PSIR images at 3T at each disc level of the spinal axis in 10 healthy subjects and measured TCA, cord diameters, WM and GM areas, and GM area/TCA ratios. Second, we investigated 32 healthy subjects at four selected levels (C2-C3, C3-C4, T8-T9, T9-T10, total acquisition time8 min) and generated normative reference values of TCA and GM areas. We assessed test-retest, intra- and interoperator reliability of the acquisition strategy, and measurement steps.The measurement procedure based on 2D PSIR imaging allowed TCA and GM area assessments along the entire spinal cord axis. The tests we performed revealed high test-retest/intraoperator reliability (mean coefficient of variation [COV] at C2-C3: TCA = 0.41%, GM area = 2.75%) and interoperator reliability of the measurements (mean COV on the 4 levels: TCA = 0.44%, GM area = 4.20%; mean intraclass correlation coefficient: TCA = 0.998, GM area = 0.906).2D PSIR allows reliable in vivo assessment of spinal cord TCA, GM, and WM areas in clinically feasible acquisition times. The area measurements presented here are in agreement with previous MRI and postmortem studies.

Published
2014

27. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

Author

Beecham, A.H., Patsopoulos, N.A., Xifara, D.K., Davis, M.F., Kemppinen, A., Cotsapas, C., Shah, T.S., Spencer, C., Booth, D., Goris, A., Oturai, A., Saarela, J., Fontaine, B., Hemmer, B., Martin, C., Zipp, F., D'Alfonso, S., Martinelli-Boneschi, F., Taylor, B., Harbo, H.F., Kockum, I., Hillert, J., Olsson, T., Ban, M., Oksenberg, J.R., Hintzen, R., Barcellos, L.F., Agliardi, C., Alfredsson, L., Alizadeh, M., Anderson, C., Andrews, R., Søndergaard, H.B., Baker, A., Band, G., Baranzini, S.E., Barizzone, N., Barrett, J., Bellenguez, C., Bergamaschi, L., Bernardinelli, L., Berthele, A., Biberacher, V., Binder, T.M.C., Blackburn, H., Bomfim, I.L., Brambilla, P., Broadley, S., Brochet, B., Brundin, L., Buck, D., Butzkueven, H., Caillier, S.J., Camu, W., Carpentier, W., Cavalla, P., Celius, E.G., Coman, I., Comi, G., Corrado, L., Cosemans, L., Cournu-Rebeix, I., Cree, B.A.C., Cusi, D., Damotte, V., Defer, G., Delgado, S.R., Deloukas, P., di Sapio, A., Dilthey, A.T., Donnelly, P., Dubois, B., Duddy, M., Edkins, S., Elovaara, I., Esposito, F., Evangelou, N., Fiddes, B., Field, J., Franke, A., Freeman, C., Frohlich, I.Y., Galimberti, D., Gieger, C., Gourraud, P-A, Graetz, C., Graham, A., Grummel, V., Guaschino, C., Hadjixenofontos, A., Hakonarson, H., Halfpenny, C., Hall, G., Hall, P., Hamsten, A., Harley, J., Harrower, T., Hawkins, C., Hellenthal, G., Hillier, C., Hobart, J., Hoshi, M., Hunt, S.E., Jagodic, M., Jelčić, I., Jochim, A., Kendall, B., Kermode, A., Kilpatrick, T., Koivisto, K., Konidari, I., Korn, T., Kronsbein, H., Langford, C., Larsson, M., Lathrop, M., Lebrun-Frenay, C., Lechner-Scott, J., Lee, M.H., Leone, M.A., Leppä, V., Liberatore, G., Lie, B.A., Lill, C.M., Linden, M., Link, J., Luessi, F., Lycke, J., Macciardi, F., Männistö, S., Manrique, C.P., Martin, R., Martinelli, V., Mason, D., Mazibrada, G., McCabe, C., Mero, I-L, Mescheriakova, J., Moutsianas, L., Myhr, K-M, Nagels, G., Nicholas, R., Nilsson, P., Piehl, F., Pirinen, M., Price, S.E., Quach, H., Reunanen, M., Robberecht, W., Robertson, N.P., Rodegher, M., Rog, D., Salvetti, M., Schnetz-Boutaud, N.C., Sellebjerg, F., Selter, R.C., Schaefer, C., Shaunak, S., Shen, L., Shields, S., Siffrin, V., Slee, M., Sorensen, P.S., Sorosina, M., Sospedra, M., Spurkland, A., Strange, A., Sundqvist, E., Thijs, V., Thorpe, J., Ticca, A., Tienari, P., van Duijn, C., Visser, E.M., Vucic, S., Westerlind, H., Wiley, J.S., Wilkins, A., Wilson, J.F., Winkelmann, J., Zajicek, J., Zindler, E., Haines, J.L., Pericak-Vance, M.A., Ivinson, A.J., Stewart, G., Hafler, D., Hauser, S.L., Compston, A., McVean, G., De Jager, P., Sawcer, S.J., McCauley, J.L., Beecham, A.H., Patsopoulos, N.A., Xifara, D.K., Davis, M.F., Kemppinen, A., Cotsapas, C., Shah, T.S., Spencer, C., Booth, D., Goris, A., Oturai, A., Saarela, J., Fontaine, B., Hemmer, B., Martin, C., Zipp, F., D'Alfonso, S., Martinelli-Boneschi, F., Taylor, B., Harbo, H.F., Kockum, I., Hillert, J., Olsson, T., Ban, M., Oksenberg, J.R., Hintzen, R., Barcellos, L.F., Agliardi, C., Alfredsson, L., Alizadeh, M., Anderson, C., Andrews, R., Søndergaard, H.B., Baker, A., Band, G., Baranzini, S.E., Barizzone, N., Barrett, J., Bellenguez, C., Bergamaschi, L., Bernardinelli, L., Berthele, A., Biberacher, V., Binder, T.M.C., Blackburn, H., Bomfim, I.L., Brambilla, P., Broadley, S., Brochet, B., Brundin, L., Buck, D., Butzkueven, H., Caillier, S.J., Camu, W., Carpentier, W., Cavalla, P., Celius, E.G., Coman, I., Comi, G., Corrado, L., Cosemans, L., Cournu-Rebeix, I., Cree, B.A.C., Cusi, D., Damotte, V., Defer, G., Delgado, S.R., Deloukas, P., di Sapio, A., Dilthey, A.T., Donnelly, P., Dubois, B., Duddy, M., Edkins, S., Elovaara, I., Esposito, F., Evangelou, N., Fiddes, B., Field, J., Franke, A., Freeman, C., Frohlich, I.Y., Galimberti, D., Gieger, C., Gourraud, P-A, Graetz, C., Graham, A., Grummel, V., Guaschino, C., Hadjixenofontos, A., Hakonarson, H., Halfpenny, C., Hall, G., Hall, P., Hamsten, A., Harley, J., Harrower, T., Hawkins, C., Hellenthal, G., Hillier, C., Hobart, J., Hoshi, M., Hunt, S.E., Jagodic, M., Jelčić, I., Jochim, A., Kendall, B., Kermode, A., Kilpatrick, T., Koivisto, K., Konidari, I., Korn, T., Kronsbein, H., Langford, C., Larsson, M., Lathrop, M., Lebrun-Frenay, C., Lechner-Scott, J., Lee, M.H., Leone, M.A., Leppä, V., Liberatore, G., Lie, B.A., Lill, C.M., Linden, M., Link, J., Luessi, F., Lycke, J., Macciardi, F., Männistö, S., Manrique, C.P., Martin, R., Martinelli, V., Mason, D., Mazibrada, G., McCabe, C., Mero, I-L, Mescheriakova, J., Moutsianas, L., Myhr, K-M, Nagels, G., Nicholas, R., Nilsson, P., Piehl, F., Pirinen, M., Price, S.E., Quach, H., Reunanen, M., Robberecht, W., Robertson, N.P., Rodegher, M., Rog, D., Salvetti, M., Schnetz-Boutaud, N.C., Sellebjerg, F., Selter, R.C., Schaefer, C., Shaunak, S., Shen, L., Shields, S., Siffrin, V., Slee, M., Sorensen, P.S., Sorosina, M., Sospedra, M., Spurkland, A., Strange, A., Sundqvist, E., Thijs, V., Thorpe, J., Ticca, A., Tienari, P., van Duijn, C., Visser, E.M., Vucic, S., Westerlind, H., Wiley, J.S., Wilkins, A., Wilson, J.F., Winkelmann, J., Zajicek, J., Zindler, E., Haines, J.L., Pericak-Vance, M.A., Ivinson, A.J., Stewart, G., Hafler, D., Hauser, S.L., Compston, A., McVean, G., De Jager, P., Sawcer, S.J., and McCauley, J.L.

Abstract

Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10−4). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10−8), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.

Published
2013

28. Modeling the cumulative genetic risk for multiple sclerosis from genome-wide association data

Author

Wang, J.H., Pappas, D., De Jager, P.L., Pelletier, D., de Bakker, P.I.W., Kappos, L., Polman, C.H., Chibnik, L.B., Hafler, D.A., Matthews, P.M., Hauser, S.L., Baranzini, S.E., Oksenberg, J.R., Kermode, A.G., Wang, J.H., Pappas, D., De Jager, P.L., Pelletier, D., de Bakker, P.I.W., Kappos, L., Polman, C.H., Chibnik, L.B., Hafler, D.A., Matthews, P.M., Hauser, S.L., Baranzini, S.E., Oksenberg, J.R., and Kermode, A.G.

Abstract

BACKGROUND: Multiple sclerosis (MS) is the most common cause of chronic neurologic disability beginning in early to middle adult life. Results from recent genome-wide association studies (GWAS) have substantially lengthened the list of disease loci and provide convincing evidence supporting a multifactorial and polygenic model of inheritance. Nevertheless, the knowledge of MS genetics remains incomplete, with many risk alleles still to be revealed. METHODS: We used a discovery GWAS dataset (8,844 samples, 2,124 cases and 6,720 controls) and a multi-step logistic regression protocol to identify novel genetic associations. The emerging genetic profile included 350 independent markers and was used to calculate and estimate the cumulative genetic risk in an independent validation dataset (3,606 samples). Analysis of covariance (ANCOVA) was implemented to compare clinical characteristics of individuals with various degrees of genetic risk. Gene ontology and pathway enrichment analysis was done using the DAVID functional annotation tool, the GO Tree Machine, and the Pathway-Express profiling tool. RESULTS: In the discovery dataset, the median cumulative genetic risk (P-Hat) was 0.903 and 0.007 in the case and control groups, respectively, together with 79.9% classification sensitivity and 95.8% specificity. The identified profile shows a significant enrichment of genes involved in the immune response, cell adhesion, cell communication/signaling, nervous system development, and neuronal signaling, including ionotropic glutamate receptors, which have been implicated in the pathological mechanism driving neurodegeneration. In the validation dataset, the median cumulative genetic risk was 0.59 and 0.32 in the case and control groups, respectively, with classification sensitivity 62.3% and specificity 75.9%. No differences in disease progression or T2-lesion volumes were observed among four levels of predicted genetic risk groups (high, medium, low, misclassified). On the othe

Published
2011

29. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

Author

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., Bang Oturai, A., 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., Martinelli Boneschi, F., 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., Rosa Guerini, F., 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., Lima Bomfim, I., 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, Salvetti, 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., 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., Bang Oturai, A., 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., Martinelli Boneschi, F., 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., Rosa Guerini, F., 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., Lima Bomfim, I., 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, Salvetti, 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., and Compston, A.

Abstract

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 disability1. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals2, 3, 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 risk4. Modestly powered genome-wide association studies (GWAS)5, 6, 7, 8, 9, 10 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 susceptibility11. 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.

Published
2011

34. A complete genomic screen for multiple sclerosis underscores a role for the major histocompatability complex

Author

Haines, J.L., primary, Ter-Minassian, M., additional, Bazyk, A., additional, Gusella, J.F., additional, Kim, D.J., additional, Terwedow, H., additional, PericakVance, M.A., additional, Rimmler, J.B., additional, Haynes, C.S., additional, Roses, A.D., additional, Lee, A., additional, Shaner, B., additional, Menold, M., additional, Seboun, E., additional, Fitoussi, R-P., additional, Gartioux, C., additional, Reyes, C., additional, Ribierre, F., additional, Gyapay, G., additional, Weissenbach, J., additional, Hauser, S.L., additional, Goodkin, D.E., additional, Lincoln, R., additional, Usuku, K., additional, Garcia-Merino, A., additional, Gatto, N., additional, Young, S., additional, and Oksenberg, J.R., additional

Published
1996
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37. Single nucleotide polymorphisms in MHC2TA, the gene encoding the MHC class II tansactivator (CIITA).

Author

Patarroyo, J.C., Stuve, O., Piskurich, J.F., Hauser, S.L., Oksenberg, J.R., and Zamvil, S.S.

Subjects
GENETIC polymorphisms, MAJOR histocompatibility complex
Abstract

Examines the polymorphisms in the promoter regions of the major histocompatibility complex class II transactivator gene. Single nucleotide polymorphism; Allele frequencies; Presence of splice variant at introns.

Published
2002
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38. Multiple sclerosis and oligodendroglioma.

Author

Green, A.J., Bollen, A.W., Berger, M.S., Oksenberg, J.R., and Hauser, S.L.

Subjects
OLIGODENDROGLIA, MULTIPLE sclerosis
Abstract

Two cases of multiple sclerosis (MS) and oligodendroglioma are reviewed, increasing the total number of reported cases to 11. In this series, the clinical onset of MS preceded the discovery of the tumor by a mean of 15 years. No distinguishing features of oligodendroglioma were characteristic of MS-associated cases. However, there was an overrepresentation of benign MS. Although this could result from biased ascertainment, other possibilities, including effective remyelination mediated by mitotically active oligodendrocytes, or secretion of immunosuppressive cytokines by the tumor tissue, cannot be excluded. It is likely that the coexistence of MS and oligodendroglioma is due to chance alone, nonetheless the possibility that glioma derived factors can moderate the disease course in MS is deserving of further study. [ABSTRACT FROM AUTHOR]

Published
2001
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39. Vitamin D in African Americans with multiple sclerosis

Author

Gelfand, J.M., Cree, B.A.C., McElroy, J., Oksenberg, J., Green, R., Mowry, E.M., Miller, J.W., Hauser, S.L., and Green, A.J.

Abstract

To evaluate whether vitamin D is associated with multiple sclerosis (MS) status and disease severity in African Americans.

Published
2011
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40. A susceptibility locus for multiple sclerosis is linked to the T cell receptor β chain complex

Author

Seboun, E., Robinson, M.A., Doolittle, T.H., Ciulla, T.A., Kindt, T.J., and Hauser, S.L.

Abstract

Inheritance of T cell receptor β chain (TCRβ) genes was analyzed in families of 40 sibling pairs concordant for the relapsing-remitting form of multiple sclerosis (MS). TCRβ haplotypes were determined by segregation analysis of polymorphic markers within the TCRβ complex. The mean proportion of TCRβ haplotypes identical by descent (IBD) inherited by MS sibling pairs was significantly increased compared with expected values (means test, p < 0.004), whereas the distribution of haplotype sharing was random when MS patients were compared with their unaffected siblings. Furthermore, one allelic form of a TCRβ variable region gene segment was overrepresented on MS chromosomes compared with those parental chromosomes not transmitted to MS offspring both in the MS sibling pair families and in a second group of families containing only one individual affected with MS. These results demonstrate that a gene within the TCRβ complex or a closely linked locus influences susceptibility to MS.

Published
1989
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42. Risk of requiring a wheelchair in primary progressive multiple sclerosis: Data from the ORATORIO trial and the MSBase registry

Author

Montalban, Xavier, Butzkueven, Helmut, Spelman, Tim, Horakova, Dana, Hughes, Stella, Solaro, Claudio Marcello, Izquierdo, Guillermo, Kubala Havrdova, Eva, Grand'Maison, Francois, Prat, Alexandre, Girard, Marc, Hupperts, Raymond, Onofrj, Marco, Lugaresi, Alessandra, Taylor, Bruce, Giovannoni, Gavin, Kappos, Ludwig, Hauser, Stephen L., Craveiro, Licinio, Freitas, Rita, Model, Fabian, Overell, James, Muros-Le Rouzic, Erwan, Sauter, Annette, Wang, Qing, Wormser, David, Wolinsky, Jerry S., MSBase Study Group, Universitat Autònoma de Barcelona, Butzkueven H., Spelman T., Horakova D., Hughes S., Solaro C., Izquierdo G., Kubala Havrdova E., Grand'Maison F., Prat A., Girard M., Hupperts R., Onofrj M., Lugaresi A., Taylor B., Giovannoni G., Kappos L., Hauser S.L., Montalban X., Craveiro L., Freitas R., Model F., Overell J., Muros-Le Rouzic E., Sauter A., Wang Q., Wormser D., and Wolinsky J.S.

Subjects
medicine.medical_specialty, Multiple Sclerosis, Primary Progressive Multiple Sclerosis, Placebo, Placebo group, 03 medical and health sciences, Primary progressive multiple sclerosis, 0302 clinical medicine, Wheelchair, ocrelizumab, wheelchair, Internal medicine, Medicine, Humans, Ocrelizumab, 030212 general & internal medicine, Registries, Disease progression, Expanded Disability Status Scale, business.industry, Multiple Sclerosis, Chronic Progressive, primary progressive multiple sclerosi, Confidence interval, Neurology, Wheelchairs, Cohort, Disease Progression, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Background and purpose: Reaching Expanded Disability Status Scale (EDSS) ≥7.0 represents the requirement for a wheelchair. Here we (i) assess the effect of ocrelizumab on time to EDSS ≥7.0 over the ORATORIO (NCT01194570) double-blind and extended controlled periods (DBP+ECP), (ii) quantify likely long-term benefits by extrapolating results, and (iii) assess the plausibility of extrapolations using an independent real-world cohort (MSBase registry; ACTRN12605000455662). Methods: Post hoc analyses assessing time to 24-week confirmed EDSS ≥7.0 in two cohorts of patients with primary progressive multiple sclerosis (baseline EDSS 3.0–6.5) were investigated in ORATORIO and MSBase. Results: In the ORATORIO DBP+ECP, ocrelizumab reduced the risk of 24-week confirmed EDSS ≥7.0 (hazard ratio=0.54, 95% confidence interval [CI]: 0.31–0.92; p=0.022). Extrapolated median time to 24-week confirmed EDSS ≥7.0 was 12.1 and 19.2years for placebo and ocrelizumab, respectively (7.1-year delay [95% CI: −4.3 to 18.4]). In MSBase, the median time to 24-week confirmed EDSS ≥7.0 was 12.4years. Conclusions: Compared with placebo, ocrelizumab significantly delayed time to 24-week confirmed wheelchair requirement in ORATORIO. The plausibility of the extrapolated median time to reach this milestone in the placebo group was supported by observed real-world data from MSBase. Extrapolated benefits for ocrelizumab over placebo could represent a truly meaningful delay in loss of ambulation and independence.

Published
2021

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