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The expanding genetic overlap between multiple sclerosis and type I diabetes

Genes & Immunity volume 10, pages 11–14 (2009)Cite this article

Abstract

Familial clustering of autoimmune disease is well recognized and raises the possibility that some susceptibility genes may predispose to autoimmunity in general. In light of this observation, it might be expected that some of the variants of established relevance in one autoimmune disease may also be relevant in other related conditions. On the basis of this hypothesis, we tested seven single nucleotide polymorphisms (SNPs) that are known to be associated with type I diabetes in a large multiple sclerosis data set consisting of 2369 trio families, 5737 cases and 10 296 unrelated controls. Two of these seven SNPs showed evidence of association with multiple sclerosis; that is rs12708716 from the CLEC16A gene (P=1.6 × 10−16) and rs763361 from the CD226 gene (P=5.4 × 10−8). These findings thereby identify two additional multiple sclerosis susceptibility genes and lend support to the notion of autoimmune susceptibility genes.

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Acknowledgements

This work was supported by the National Multiple Sclerosis Society (AP 3758-A-16, RG 2899 and FG-1718-A1), grants from the NINDS (NS049477, NS032830 and NS26799), AI067152, the NIAID (P01 AI039671), an NMSS Collaborative Research Award (CA 1001-A-14) and the Penates Foundation. We acknowledge use of DNA from the British 1958 Birth Cohort collection, funded by the Medical Research Council Grant G0000934 and the Wellcome Trust Grant 068545/Z/02. The 1958 Birth Cohort samples were typed by John Todd and his group, and the resulting data made available by Neil Walker, we thank all the members of this team for generously providing these data. The Norwegian Bone Marrow Donor Registry is acknowledged for collaboration in establishment of the Norwegian control material. The Swedish sample was collected and analysed with the help of grants from the European Union fp6 program—NeuroproMiSe (LSHM-CT-2005-018637) and the Bibbi and Nils Jensens foundation. The Australian National Health and Medical Research Council is acknowledged for funding the collection and analysis of the Australian samples. AG is a Postdoctora Fellow and BD a Clinical Investigator of the Research Foundation Flanders (FWO-Vlaanderen). ARL is supported by The Research Council of Norway (166005/V5) and Odd Fellow MS society. We also thank the many healthy controls, multiple sclerosis patients and their families who participated in this study.

Author information

Author notes

  1. Dr M Ban, Neurology Unit, Department of Clinical Neuroscience, University of Cambridge, Addenbrooke's Hospital, Box 165, Hills Road, Cambridge CB2 2QQ, UK. E-mail: mb531@medschl.cam.ac.uk

Consortia

International Multiple Sclerosis Genetics Consortium (IMSGC)

  • David R Booth
  • , Robert N Heard
  • , Graeme J Stewart
  • , An Goris
  • , Rita Dobosi
  • , Bénédicte Dubois
  • , Åslaug R Lorentzen
  • , Elisabeth G Celius
  • , Hanne F Harbo
  • , Anne Spurkland
  • , Tomas Olsson
  • , Ingrid Kockum
  • , Jenny Link
  • , Jan Hillert
  • , Maria Ban
  • , Amie Baker
  • , Stephen Sawcer
  • , Alastair Compston
  • , Tania Mihalova
  • , Richard Strange
  • , Clive Hawkins
  • , Gillian Ingram
  • , Neil P Robertson
  • , Philip L De Jager
  • , David A Hafler
  • , Lisa F Barcellos
  • , Adrian J Ivinson
  • , Margaret Pericak-Vance
  • , Jorge R Oksenberg
  • , Stephen L Hauser
  • , Jacob L McCauley
  • , David Sexton
  •  & Jonathan Haines

Additional information

Contributors Australia David R Booth, Robert N Heard, Graeme J Stewart University of Sydney, Institute for Immunology and Allergy Research, Westmead Millennium Institute, Westmead Hospital, NSW 2145, Australia Belgium An Goris, Rita Dobosi, Bénédicte Dubois Section for Experimental Neurology, Katholieke Universiteit Leuven, Leuven 3000, Belgium. Norway Åslaug R Lorentzen Department of Neurology, Faculty Division Ullevål University Hospital, University of Oslo, Oslo, Norway, and Institute of Immunology, Rikshospitalet University Hospital, Oslo N-0027, Norway Elisabeth G Celius, Hanne F Harbo Department of Neurology, Ullevål University Hospital, Oslo N-0407, Norway Anne Spurkland Institute of Basal Medical Sciences, University of Oslo, Blindern, Oslo N-0317, Norway Sweden Tomas Olsson, Ingrid Kockum, Jenny Link, Jan Hillert Department of Clinical Neurosciences, Center for Molecular Medicine CMM, L8:04, Karolinska Hospital, Stockholm 171 76, Sweden United Kingdom Maria Ban, Amie Baker, Stephen Sawcer, Alastair Compston Department of Clinical Neuroscience, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK Tania Mihalova, Richard Strange, Clive Hawkins Department of Neurology and Human Genomics, Keele University Medical School, Hartshill Campus, Stoke on Trent ST4 7LN, UK Gillian Ingram, Neil P Robertson Department of Neurology, University Hospital of Wales, Heath Park, Cardiff CF14 4XW, UK. United States Philip L De Jager, David A Hafler Division of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA, USA, and Harvard Medical School/Partners Healthcare Center for Genetics and Genomics, Boston, MA, USA Lisa F Barcellos University of California at Berkeley, Berkeley, CA, USA Adrian J Ivinson Harvard NeuroDiscovery Center, Harvard Medical School, Boston, MA, USA. Margaret Pericak-Vance University of Miami School of Medicine, Miami, FL, USA Jorge R Oksenberg, Stephen L Hauser Department of Neurology, University of California San Francisco, San Francisco, CA, USA Jacob L McCauley, David Sexton, Jonathan Haines Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, USA.

Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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International Multiple Sclerosis Genetics Consortium (IMSGC). The expanding genetic overlap between multiple sclerosis and type I diabetes. Genes Immun 10, 11–14 (2009). https://doi.org/10.1038/gene.2008.83

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