Skip to content

Research at St Andrews

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

Research output: Contribution to journalArticle

DOI

Author(s)

Ashley H Beecham, Nikolaos A Patsopoulos, Dionysia K Xifara, Mary F Davis, Anu Kemppinen, Chris Cotsapas, Tejas S Shah, Chris Spencer, David Booth, An Goris, Annette Oturai, Janna Saarela, Bertrand Fontaine, Bernhard Hemmer, Claes Martin, Frauke Zipp, Sandra D'Alfonso, Filippo Martinelli-Boneschi, Bruce Taylor, Hanne F Harbo & 31 others Ingrid Kockum, Jan Hillert, Tomas Olsson, Maria Ban, Jorge R Oksenberg, Rogier Hintzen, Lisa F Barcellos, Cristina Agliardi, Lars Alfredsson, Mehdi Alizadeh, Carl Anderson, Robert Andrews, Helle Bach Søndergaard, Amie Baker, Gavin Band, Sergio E Baranzini, Nadia Barizzone, Jeffrey Barrett, Céline Bellenguez, Laura Bergamaschi, Luisa Bernardinelli, Achim Berthele, Viola Biberacher, Thomas M C Binder, Hannah Blackburn, Izaura L Bomfim, Paola Brambilla, Simon Broadley, Bruno Brochet, John Zajicek, International Multiple Sclerosis Genetics Consortium (IMSGC)

School/Research organisations

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.

Close

Details

Original languageEnglish
Pages (from-to)1353-60
Number of pages8
JournalNature Genetics
Volume45
Issue number11
DOIs
Publication statusPublished - Nov 2013

    Research areas

  • Chromosome Mapping, European Continental Ancestry Group, Gene Frequency, Genetic Loci, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Multiple Sclerosis, Polymorphism, Single Nucleotide

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Assessment of a home-based standing frame programme in people with progressive multiple sclerosis (SUMS): a pragmatic, multi-centre, randomised, controlled trial and cost-effectiveness analysis

    Freeman, J. A., Hendrie, W., Jarrett, L., Hawton, A., Barton, A., Dennett, R., Jones, B., Zajicek, J. P. & Creanor, S., 1 Aug 2019, In : Lancet Neurology. 18, 8, p. 736-747

    Research output: Contribution to journalArticle

  2. Machine-learning based identification of undiagnosed dementia in primary care: a feasibility study

    Jammeh, E. A., Carroll, C. B., Pearson, S. W., Escudero, J., Anastasiou, A., Zhao, P., Chenore, T., Zajicek, J. & Ifeachor, E., 12 Jun 2018, In : BJGP Open. 2, 2, 13 p., bjgpopen18X101589.

    Research output: Contribution to journalArticle

  3. Improving the quality of cognitive screening assessments: ACEmobile, an iPad-based version of the Addenbrooke's Cognitive Examination-III

    Newman, C. G. J., Bevins, A. D., Zajicek, J. P., Hodges, J. R., Vuillermoz, E., Dickenson, J. M., Kelly, D. S., Brown, S. & Noad, R. F., 2018, In : Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. 10, p. 182-187 6 p.

    Research output: Contribution to journalArticle

  4. Balance Right in Multiple Sclerosis (BRiMS): a guided self-management programme to reduce falls and improve quality of life, balance and mobility in people with secondary progressive multiple sclerosis: a protocol for a feasibility randomised controlled trial

    Gunn, H., Andrade, J., Paul, L., Miller, L., Creanor, S., Green, C., Marsden, J., Ewings, P., Berrow, M., Vickery, J., Barton, A., Marshall, B., Zajicek, J. & Freeman, J. A., 27 Jul 2017, In : Pilot and Feasibility Studies. 4, 12 p., 26.

    Research output: Contribution to journalArticle

  5. Time-and region-specific season of birth effects in multiple sclerosis in the United Kingdom

    Cruz, P. M. R., Matthews, L., Boggild, M., Cavey, A., Constantinescu, C. S., Evangelou, N., Giovannoni, G., Gray, O., Hawkins, S., Nicholas, R., Oppenheimer, M., Robertson, N., Zajicek, J., Rothwell, P. M. & Palace, J., 1 Aug 2016, In : JAMA Neurology. 73, 8, p. 954-960 7 p.

    Research output: Contribution to journalArticle

Related by journal

  1. Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics

    Davies, M. R., McIntyre, L., Mutreja, A., Lacey, J. A., Lees, J. A., Towers, R. J., Duchêne, S., Smeesters, P. R., Frost, H. R., Price, D. J., Holden, M. T. G., David, S., Giffard, P. M., Worthing, K. A., Seale, A. C., Berkley, J. A., Harris, S. R., Rivera-Hernandez, T., Berking, O., Cork, A. J. & 18 others, Torres, R. S. L. A., Lithgow, T., Strugnell, R. A., Bergmann, R., Nitsche-Schmitz, P., Chhatwal, G. S., Bentley, S. D., Fraser, J. D., Moreland, N. J., Carapetis, J. R., Steer, A. C., Parkhill, J., Saul, A., Williamson, D. A., Currie, B. J., Tong, S. Y. C., Dougan, G. & Walker, M. J., Jun 2019, In : Nature Genetics. 51, 6, p. 1035-1043

    Research output: Contribution to journalArticle

  2. Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets

    Wedge, D. C., Gundem, G., Mitchell, T., Woodstock, D. J., Martincorena, I., Ghori, M., Zamora, J., Butler, A., Whitaker, H., Kote-Jarai, Z., Alexandrov, L. B., Van Loo, P., Massie, C. E., Dentro, S., Warren, A. Y., Verrill, C., Berney, D. M., Dennis, N., Merson, S., Hawkins, S. & 68 others, Howat, W., Lu, Y-J., Lambert, A., Kay, J., Kremeyer, B., Karaszi, K., Camacho, N., Luxton, H., Marsden, L., Edwards, S., Matthews, L., Bo, V., Leongamornlert, D., McLaren, S., Ng, A., Yu, Y., Zhang, H., Dadaev, T., Thomas, S., Easton, D. F., Ahmed, M., Bancroft, E., Fisher, C., Livni, N., Nicol, D., Tavaré, S., Gill, P., Greenman, C., Khoo, V., Van As, N., Kumar, P., Ogden, C., Cahill, D., Thompson, A., Mayer, E., Rowe, E., Dudderidge, T., Gnanapragasam, V., Shah, N. C., Raine, K., Jones, D., Menzies, A., Stebbings, L., Teague, J., Hazell, S., Corbishley, C., CamCaP Study Group, de Bono, J., Attard, G., Isaacs, W., Visakorpi, T., Fraser, M., Boutros, P. C., Bristow, R. G., Workman, P., Sander, C., The TCGA Consortium, Hamdy, F. C., Futreal, A., McDermott, U., Al-Lazikani, B., Lynch, A., Bova, G. S., Foster, C. S., Brewer, D. S., Neal, D. E., Cooper, C. S. & Eeles, R. A., 16 Apr 2018, In : Nature Genetics. 50, p. 682-692 16 p.

    Research output: Contribution to journalArticle

  3. Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance

    Secrier, M., Li, X., de Silva, N., Eldridge, M. D., Contino, G., Bornschein, J., MacRae, S., Grehan, N., O'Donovan, M., Miremadi, A., Yang, T-P., Bower, L., Chettouh, H., Crawte, J., Galeano-Dalmau, N., Grabowska, A., Saunders, J., Underwood, T., Waddell, N., Barbour, A. P. & 7 others, Nutzinger, B., Achilleos, A., Edwards, P. A. W., Lynch, A. G., Tavaré, S., Fitzgerald, R. C. & Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium, 5 Sep 2016, In : Nature Genetics. 48, 10, p. 1131-1141 11 p.

    Research output: Contribution to journalArticle

  4. Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue

    Cooper, C. S., Eeles, R., Wedge, D. C., Van Loo, P., Gundem, G., Alexandrov, L. B., Kremeyer, B., Butler, A., Lynch, A. G., Camacho, N., Massie, C. E., Kay, J., Luxton, H. J., Edwards, S., Kote-Jarai, Z., Dennis, N., Merson, S., Leongamornlert, D., Zamora, J., Corbishley, C. & 51 others, Thomas, S., Nik-Zainal, S., O'Meara, S., Matthews, L., Clark, J., Hurst, R., Mithen, R., Bristow, R. G., Boutros, P. C., Fraser, M., Cooke, S., Raine, K., Jones, D., Menzies, A., Stebbings, L., Hinton, J., Teague, J., McLaren, S., Mudie, L., Hardy, C., Anderson, E., Joseph, O., Goody, V., Robinson, B., Maddison, M., Gamble, S., Greenman, C., Berney, D., Hazell, S., Livni, N., Fisher, C., Ogden, C., Kumar, P., Thompson, A., Woodhouse, C., Nicol, D., Mayer, E., Dudderidge, T., Shah, N. C., Gnanapragasam, V., Voet, T., Campbell, P., Futreal, A., Easton, D., Warren, A. Y., Foster, C. S., Stratton, M. R., Whitaker, H. C., McDermott, U., Brewer, D. S. & Neal, D. E., 28 Apr 2015, In : Nature Genetics. 47, 4, p. 367-372 6 p.

    Research output: Contribution to journalArticle

  5. Whole-genome sequencing provides new insights into the clonal architecture of Barrett's esophagus and esophageal adenocarcinoma

    Ross-Innes, C. S., Becq, J., Warren, A., Cheetham, R. K., Northen, H., O'Donovan, M., Malhotra, S., Di Pietro, M., Ivakhno, S., He, M., Weaver, J. M. J., Lynch, A. G., Kingsbury, Z., Ross, M., Humphray, S., Bentley, D., Fitzgerald, R. C., Hayes, S. J., Ang, Y., Welch, I. & 85 others, Preston, S., Oakes, S., Save, V., Skipworth, R., Tucker, O., Davies, J., Crichton, C., Schusterreiter, C., Underwood, T., Noble, F., Stacey, B., Kelly, J., Byrne, J., Haydon, A., Sharland, D., Owsley, J., Barr, H., Lagergren, J., Gossage, J., Davies, A., Mason, R., Chang, F., Zylstra, J., Sanders, G., Wheatley, T., Berrisford, R., Bracey, T., Harden, C., Bunting, D., Roques, T., Nobes, J., Loo, S., Lewis, M., Cheong, E., Priest, O., Parsons, S. L., Soomro, I., Kaye, P., Saunders, J., Pang, V., Welch, N., Catton, J. A., Duffy, J. P., Ragunath, K., Lovat, L., Haidry, R., Miah, H., Kerr, S., Eneh, V., Butawan, R., Lewis, M., Cheong, E., Kumar, B., Igali, L., Walton, S., Dann, A., Safranek, P., Hindmarsh, A., Sudjendran, V., Scott, M., Cluroe, A., Miremadi, A., Mahler-Araujo, B., Nutzinger, B., Peters, C., Abdullahi, Z., Crawte, J., MacRae, S., Noorani, A., Elliott, R. F., Bower, L., Edwards, P., Tavare, S., Eldridge, M., Bornschein, J., Secrier, M., Yang, T. P., O'Neill, J. R., Adamczuk, K., Lao-Sirieix, P., Grehan, N., Smith, L., Lishman, S., Beardsmore, D. & Dawson, S., 27 Aug 2015, In : Nature Genetics. 47, 9, p. 1038-1046 9 p.

    Research output: Contribution to journalArticle

ID: 242547172

Top