Article abstract
Nature Genetics 41, 776 - 782 (2009)
Published online: 14 June 2009 | doi:10.1038/ng.401
Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci
Philip L De Jager1,2,3, Xiaoming Jia4, Joanne Wang5,6, Paul I W de Bakker3,4, Linda Ottoboni1,2,3, Neelum T Aggarwal7, Laura Piccio8, Soumya Raychaudhuri3,9, Dong Tran3, Cristin Aubin3, Rebeccah Briskin2, Susan Romano1, International MS Genetics Consortium, Sergio E Baranzini5, Jacob L McCauley10, Margaret A Pericak-Vance10, Jonathan L Haines11, Rachel A Gibson12, Yvonne Naeglin13, Bernard Uitdehaag14, Paul M Matthews12, Ludwig Kappos13, Chris Polman14, Wendy L McArdle15, David P Strachan16, Denis Evans7, Anne H Cross8, Mark J Daly3,17, Alastair Compston18, Stephen J Sawcer18, Howard L Weiner1, Stephen L Hauser5,6,19, David A Hafler1,3,19 & Jorge R Oksenberg5,6,19
Abstract
We report the results of a meta-analysis of genome-wide association scans for multiple sclerosis (MS) susceptibility that includes 2,624 subjects with MS and 7,220 control subjects. Replication in an independent set of 2,215 subjects with MS and 2,116 control subjects validates new MS susceptibility loci at TNFRSF1A (combined P = 1.59 
10-11), IRF8 (P = 3.73 10-9) and CD6 (P = 3.79 10-9). TNFRSF1A harbors two independent susceptibility alleles: rs1800693 is a common variant with modest effect (odds ratio = 1.2), whereas rs4149584 is a nonsynonymous coding polymorphism of low frequency but with stronger effect (allele frequency = 0.02; odds ratio = 1.6). We also report that the susceptibility allele near IRF8, which encodes a transcription factor known to function in type I interferon signaling, is associated with higher mRNA expression of interferon-response pathway genes in subjects with MS.
- Division of Molecular Immunology, Center for Neurologic Diseases, Department of Neurology, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
- Partners Center for Personalized Genetic Medicine, Boston, Massachusetts, USA.
- Program in Medical & Population Genetics, Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
- Division of Genetics, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
- Department of Neurology and Institute for Human Genetics, School of Medicine, University of California, San Francisco, San Francisco, California, USA.
- Institute for Human Genetics, School of Medicine, University of California, San Francisco, San Francisco, California, USA.
- Rush Alzheimer Disease Center & Department of Neurological Sciences, Rush University, Chicago, Illinois, USA.
- Department of Neurology, Washington University, St. Louis, Missouri, USA.
- Division of Immunology, Allergy and Rheumatology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
- Miami Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida, USA.
- Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
- GlaxoSmithKline Clinical Imaging Centre, Hammersmith Hospital and Department of Clinical Neurosciences, Imperial College, London.
- Department of Neurology, University Hospital Basel, Basel, Switzerland.
- Department of Neurology, Vrije Universiteit Medical Centre, Amsterdam, The Netherlands.
- Department of Social Medicine, University of Bristol, Bristol, UK.
- Division of Community Health sciences, St. George's, University of London, London, UK.
- Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.
- University of Cambridge, Department of Clinical Neurosciences, Addenbrooke's Hospital, Cambridge, UK.
- These authors contributed equally to this work.
Correspondence to: Philip L De Jager1,2,3 e-mail: pdejager@rics.bwh.harvard.edu
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
Confronting ethnicity-specific disease riskNature Genetics News and Views (01 Jan 2006)
RESEARCH
Expert assessment of exposure to carcinogens in Norway's offshore petroleum industryJournal of Exposure Science and Environmental Epidemiology Article Response
The c-Ha-ras1, insulin and β-globin loci map outside the deletion associated with aniridia-Wilms' tumourNature Letters to Editor (13 Oct 1983)
Six new loci associated with body mass index highlight a neuronal influence on body weight regulationNature Genetics Article (01 Jan 2009)
See all 61 matches for Research
