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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis
University of Miami, FL USA .
Brigham and Womens Hospital, MA USA .
University of Oxford, England .
Vanderbilt University, TN USA .
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2013 (English)In: Nature Genetics, ISSN 1061-4036, Vol. 45, no 11, 1353-+ p.Article in journal (Refereed) Published
Abstract [en]

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 andlt; 1.0 x 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 andlt; 5.0 x 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.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA , 2013. Vol. 45, no 11, 1353-+ p.
National Category
Engineering and Technology
URN: urn:nbn:se:liu:diva-102079DOI: 10.1038/ng.2770ISI: 000326384100016OAI: diva2:669010

Funding Agencies|US National Institutes of Health||Wellcome Trust||UK MS Society||UK Medical Research Council||US National MS Society||Cambridge National Institute for Health Research (NIHR) Biomedical Research Centre||DeNDRon||Swedish Brain Foundation||Swedish Research Council||Knut and Alice Wallenberg Foundation||Swedish Heart-Lung Foundation||Foundation for Strategic Research||

Available from: 2013-12-02 Created: 2013-11-29 Last updated: 2013-12-02

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