Journal article

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

AH Beecham, NA Patsopoulos, DK Xifara, MF Davis, A Kemppinen, C Cotsapas, TS Shah, C Spencer, D Booth, A Goris, A Oturai, J Saarela, B Fontaine, B Hemmer, C Martin, F Zipp, S D'Alfonso, F Martinelli-Boneschi, B Taylor, HF Harbo Show all

Nature Genetics | Published : 2013

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 outs..

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Grants

Awarded by National Cancer Institute


Funding Acknowledgements

We thank the participants, the referring nurses, the physicians and the funders. Funding was provided by the US National Institutes of Health, the Wellcome Trust, the UK MS Society, the UK Medical Research Council, the US National MS Society, the Cambridge National Institute for Health Research (NIHR) Biomedical Research Centre, DeNDRon, the Bibbi and Niels Jensens Foundation, the Swedish Brain Foundation, the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the Swedish Heart-Lung Foundation, the Foundation for Strategic Research, the Stockholm County Council, Karolinska Institutet, INSERM, Fondation d'Aide pour la Recherche sur la Sclerose en Plaques, Association Francaise contre les Myopathies, Infrastrutures en Biologie Sante et Agronomie (GIS-IBISA), the German Ministry for Education and Research, the German Competence Network MS, Deutsche Forschungsgemeinschaft, Munich Biotec Cluster M4, the Fidelity Biosciences Research Initiative, Research Foundation Flanders, Research Fund KU Leuven, the Belgian Charcot Foundation, Gemeinnutzige Hertie Stiftung, University Zurich, the Danish MS Society, the Danish Council for Strategic Research, the Academy of Finland, the Sigrid Juselius Foundation, Helsinki University, the Italian MS Foundation, Fondazione Cariplo, the Italian Ministry of University and Research, the Torino Savings Bank Foundation, the Italian Ministry of Health, the Italian Institute of Experimental Neurology, the MS Association of Oslo, the Norwegian Research Council, the South- Eastern Norwegian Health Authorities, the Australian National Health and Medical Research Council, the Dutch MS Foundation and Kaiser Permanente. We acknowledge the British 1958 Birth Cohort, the UK National Blood Service, Vanderbilt University Medical Center's BioVU DNA Resources Core, Centre de Ressources Biologiques du Reseau Francais d'Etude Genetique de la Sclorose en Plaques, the Norwegian Bone Marrow Registry, the Norwegian MS Registry and Biobank, the North American Research Committee on MS Registry, the Brigham and Women's Hospital PhenoGenetic Project and DILGOM, funded by the Academy of Finland. See the Supplementary Note for details.