Regulatory genomic regions active in immune cell types explain a large proportion of the genetic risk of multiple sclerosis

Journal of Human Genetics

Volumn 59, Issue 4, 2014, Pages 211-215

  Elangovan, Ramyiadarsini I ^a   Disanto, Giulio ^a,b   Berlanga Taylor, Antonio J ^a   Ramagopalan, Sreeram V ^a,b   Handunnetthi, Lahiru ^a  

^a MEDICAL RESEARCH COUNCIL   (United Kingdom)

^b QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

Cellular immunity; Chromatin profile; DNase hypersensitivity site; Multiple sclerosis; Single nucleotide polymorphism

Indexed keywords

DEOXYRIBONUCLEASE; CHROMATIN; DEOXYRIBONUCLEASE I;

ARTICLE; B LYMPHOCYTE; CASE CONTROL STUDY; CELL SPECIFICITY; CELL TYPE; CELLULAR IMMUNITY; CHROMATIN; CONTROLLED STUDY; ENHANCER REGION; GENETIC ASSOCIATION; GENETIC RISK; GENOTYPE; HUMAN; HUMAN CELL; IMMUNOCOMPETENT CELL; MAJOR CLINICAL STUDY; MULTIPLE SCLEROSIS; SINGLE NUCLEOTIDE POLYMORPHISM; GENETIC PREDISPOSITION; GENETIC VARIABILITY; GENETICS; HEPG2 CELL LINE; IMMUNOLOGY; KERATINOCYTE; METABOLISM; REGULATORY SEQUENCE; RISK FACTOR;

B-LYMPHOCYTES; CASE-CONTROL STUDIES; CHROMATIN; DEOXYRIBONUCLEASE I; ENHANCER ELEMENTS, GENETIC; GENETIC PREDISPOSITION TO DISEASE; GENETIC VARIATION; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE; HEP G2 CELLS; HUMANS; KERATINOCYTES; MULTIPLE SCLEROSIS; POLYMORPHISM, SINGLE NUCLEOTIDE; REGULATORY SEQUENCES, NUCLEIC ACID; RISK FACTORS;

EID: 84899544568     PISSN: 14345161     EISSN: 1435232X     Source Type: Journal    
DOI: 10.1038/jhg.2014.3     Document Type: Article

References (27)

1. Compston, A. & Coles, A. Multiple sclerosis. Lancet 372, 1502-1517 (2008
2. Ebers, G. C., Sadovnick, A. D. & Risch, N. J. Canadian Collaborative Study Group. A genetic basis for familial aggregation in multiple sclerosis. Nature 377, 150-151 (1995
3. Willer, C. J., Dyment, D. A., Risch, N. J., Sadovnick, A. D. & Ebers, G. C. Twin concordance and sibling recurrence rates in multiple sclerosis. Proc. Natl Acad. Sci. USA 100, 12877-12882 (2003
4. Ramagopalan, S. V. & Ebers, G. C. Multiple sclerosis: Major histocompatibility complexity and antigen presentation. Genome Med. 1, 105 (2009
5. International multiple sclerosis genetics consortium (IMSGC), Beecham, A. H., Patsopoulos, N. A., Xifara, D. K., Davis, M. F., Kemppinen, A. et al. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat. Genet. 45, 1353-1360 (2013
6. Ernst, J., Kheradpour, P., Mikkelsen, T. S., Shoresh, N., Ward, L. D., Epstein, C. B. et al. Mapping and analysis of chromatin state dynamics in nine human cell types. Nature 473, 43-49 (2011
7. Maurano, M. T., Humbert, R., Rynes, E., Thurman, R. E., Haugen, E., Wang, H. et al. Systematic localization of common disease-Associated variation in regulatory DNA. Science 337, 1190-1195 (2012
8. Sheffield, N. C., Thurman, R. E., Song, L., Safi, A., Stamatoyannopuolos, J. A., Lenhard, B. et al. Patterns of regulatory activity across diverse human cell types predict tissue identity, transcription factor binding, and long-range interactions. Genome Res. 23, 777-788 (2013
9. Watson, C. T., Disanto, G., Breden, F., Giovannoni, G. & Ramagopalan, S. V. Estimating the proportion of variation in susceptibility to multiple sclerosis captured by common SNPs. Sci. Rep. 2, 770 (2012
10. Yang, J., Lee, S. H., Goddard, M. E. & Visscher, P. M. GCTA: A tool for genome-wide complex trait analysis. Am. J. Hum. Genet. 88, 76-82 (2011
11. Lee, S. H., Wray, N. R., Goddard, M. E. & Visscher, P. M. Estimating missing heritability for disease from genome-wide association studies. Am. J. Hum. Genet. 88, 294-305 (2011
12. Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A., Bender, D. et al. PLINK: A tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559-575 (2007
13. Boyle, A. P., Hong, E. L., Hariharan, M., Cheng, Y., Schaub, M. A., Kasowski, M. et al. Annotation of functional variation in personal genomes using RegulomeDB. Genome Res. 22, 1790-1797 (2007
14. Sawalha, A. H., Hughes, T., Nadig, A., Vuslat, Y., Kenan, A., Gokhan, K. et al. A putative functional variant within the UBAC2 gene is associated with increased risk of Behcet-s disease. Arthritis. Rheum. 63, 3607-3612 (2011
15. Hou, S., Shu, Q., Jiang, Z., Chen, Y., Li, F., Chen, F. et al. Replication study confirms the association between UBAC2 and Behcet-s disease in two independent Chinese sets of patients and controls. Arthritis Res. Ther. 14, R70 (2012
16. Dubois, P. C., Trynka, G., Franke, L., Hunt, K. A., Romanos, J., Curtotti, A. et al. Multiple common variants for celiac disease influencing immune gene expression. Nat. Genet. 42, 295-302 (2010
17. International Multiple Sclerosis Genetics Consortium. Comprehensive follow-up of the first genome-wide association study of multiple sclerosis identifies KIF21B and TMEM39A as susceptibility loci. Hum. Mol. Genet. 19, 953-962 (2010
18. Leikfoss, I. S., Mero, I. L., Dahle, M. K., Lie, B. A., Harbo, H. F., Spurkland, A. et al. Multiple sclerosis-Associated single-nucleotide polymorphisms in CLEC16A correlate with reduced SOCS1 and DEXI expression in the thymus. Genes Immun. 14, 62-66 (2013
19. Freedman, M. S., Thompson, E. J., Deisenhammer, F., Giovanonni, G., Grimsley, G., Keir, G. et al. Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple sclerosis: A consensus statement. Arch. Neurol. 62, 865-870 (2005
20. Disanto, G., Morahan, J. M., Barnett, M. H., Giovannoni, G. & Ramagopalan, S. V. The evidence for a role of B cells in multiple sclerosis. Neurology 78, 823-832 (2012
21. Howell, O. W., Reeves, C. A., Nicholas, R., Carrassiti, D., Roncaroli, F., Magliozzi, R. et al. Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis. Brain 134, 2755-2771 (2011
22. Brettschneider, J., Czerwoniak, A., Senel, M., Fang, L., Kassubeck, J., Pinkhardt, E. et al. The chemokine CXCL13 is a prognostic marker in clinically isolated syndrome (CIS). PLoS One 5, e11986 (2010
23. Brettschneider, J., Tumani, H., Kiechle, U., Muche, R., Richards, G., Lehmensiek, V. et al. IgG antibodies against measles, rubella, and varicella zoster virus predict conversion to multiple sclerosis in clinically isolated syndrome. PLoS One 4, e7638 (2009
24. Joseph, F. G., Hirst, C. L., Pickersgill, T. P., Ben-Shlomo, Y., Robertson, N. P. & Scolding, N. J. CSF oligoclonal band status informs prognosis in multiple sclerosis: A case control study of 100 patients. J Neurol. Neurosurg. Psychiatry 80, 292-296 (2009
25. Khademi, M., Kockum, I., Andersson, M. L., Iaocobaeus, E., Brundin, L., Sellebjerg, F. et al. Cerebrospinal fluid CXCL13 in multiple sclerosis: A suggestive prognostic marker for the disease course. Mult. Scler. 17, 335-343 (2011
26. Hauser, S. L., Waubant, E., Arnold, D. L., Vollmer, T., Antel, J., Fox, R. J. et al. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N. Engl. J. Med. 358, 676-688 (2008
27. Kappos, L., Li, D., Calabresi, P. A., O-Connor, P., Bar-Or, A., Barkhof, F. et al. Ocrelizumab in relapsing-remitting multiple sclerosis: A phase 2, randomised, placebocontrolled, multicentre trial. Lancet 378, 1779-1787 (2011.