دورية أكاديمية
Genetic variants are major determinants of CSF antibody levels in multiple sclerosis
| العنوان: | Genetic variants are major determinants of CSF antibody levels in multiple sclerosis |
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| المؤلفون: | Goris, An, Pauwels, Ine, Gustavsen, Marte W, van Son, Brechtje, Hilven, Kelly, Bos, Steffan D, Celius, Elisabeth Gulowsen, Berg-Hansen, Pal, Aarseth, Jan, Myhr, Kjell-Morten, D'Alfonso, Sandra, Barizzone, Nadia, Leone, Maurizio A, Boneschi, Filippo Martinelli, Sorosina, Melissa, Liberatore, Giuseppe, Kockum, Ingrid, Olsson, Tomas, Hillert, Jan, Alfredsson, Lars, Bedri, Sahl Khalid, Hemmer, Bernhard, Buck, Dorothea, Berthele, Achim, Knier, Benjamin, Biberacher, Viola, van Pesch, Vincent, Sindic, Christian, Oturai, Annette Bang, Sondergaard, Helle Bach, Sellebjerg, Finn, Jensen, Poul Erik H, Comabella, Manuel, Montalban, Xavier, Perez-Boza, Jennifer, Malhotra, Sunny, Lechner-Scott, Jeannette, Broadley, Simon, Slee, Mark, Taylor, Bruce, Kermode, Allan G, Gourraud, Pierre-Antoine, Sawcer, Stephen J, Andreassen, Bettina Kullle, Dubois, Benedicte, Harbo, Hanne F |
| بيانات النشر: | Oxford University Press |
| سنة النشر: | 2015 |
| المجموعة: | Griffith University: Griffith Research Online |
| مصطلحات موضوعية: | Biomedical and clinical sciences, Psychology |
| الوصف: | Immunological hallmarks of multiple sclerosis include the production of antibodies in the central nervous system, expressed as presence of oligoclonal bands and/or an increased immunoglobulin G index—the level of immunoglobulin G in the cerebrospinal fluid compared to serum. However, the underlying differences between oligoclonal band-positive and -negative patients with multiple sclerosis and reasons for variability in immunoglobulin G index are not known. To identify genetic factors influencing the variation in the antibody levels in the cerebrospinal fluid in multiple sclerosis, we have performed a genome-wide association screen in patients collected from nine countries for two traits, presence or absence of oligoclonal bands (n = 3026) and immunoglobulin G index levels (n = 938), followed by a replication in 3891 additional patients. We replicate previously suggested association signals for oligoclonal band status in the major histocompatibility complex region for the rs9271640*A-rs6457617*G haplotype, correlated with HLA-DRB1*1501, and rs34083746*G, correlated with HLA-DQA1*0301 (P comparing two haplotypes = 8.88 × 10−16). Furthermore, we identify a novel association signal of rs9807334, near the ELAC1/SMAD4 genes, for oligoclonal band status (P = 8.45 × 10−7). The previously reported association of the immunoglobulin heavy chain locus with immunoglobulin G index reaches strong evidence for association in this data set (P = 3.79 × 10−37). We identify two novel associations in the major histocompatibility complex region with immunoglobulin G index: the rs9271640*A-rs6457617*G haplotype (P = 1.59 × 10−22), shared with oligoclonal band status, and an additional independent effect of rs6457617*G (P = 3.68 × 10−6). Variants identified in this study account for up to 2-fold differences in the odds of being oligoclonal band positive and 7.75% of the variation in immunoglobulin G index. Both traits are associated with clinical features of disease such as female gender, age at onset and severity. This is the largest ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0006-8950 |
| العلاقة: | Brain; http://hdl.handle.net/10072/141948Test |
| DOI: | 10.1093/brain/awu405 |
| الإتاحة: | https://doi.org/10.1093/brain/awu405Test http://hdl.handle.net/10072/141948Test |
| حقوق: | © 2015 Oxford University Press. This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Brain following peer review. The definitive publisher-authenticated version Genetic variants are major determinants of CSF antibody levels in multiple sclerosis, Brain, Volume 138, Issue 3, 2015, Pages 632–643 is available online at: https://doi.org/10.1093/brain/awu405Test. ; open access |
| رقم الانضمام: | edsbas.97208F95 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00068950 |
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| DOI: | 10.1093/brain/awu405 |