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- Title
Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci.
- Authors
De Jager, Philip L; Jia, Xiaoming; Wang, Joanne; de Bakker, Paul I W; Ottoboni, Linda; Aggarwal, Neelum T; Piccio, Laura; Raychaudhuri, Soumya; Tran, Dong; Aubin, Cristin; Briskin, Rebeccah; Romano, Susan; Baranzini, Sergio E; McCauley, Jacob L; Pericak-Vance, Margaret A; Haines, Jonathan L; Gibson, Rachel A; Naeglin, Yvonne; Uitdehaag, Bernard; Matthews, Paul M; Kappos, Ludwig; Polman, Chris; McArdle, Wendy L; Strachan, David P; Evans, Denis; Cross, Anne H; Daly, Mark J; Compston, Alastair; Sawcer, Stephen J; Weiner, Howard L; Hauser, Stephen L; Hafler, David A; Oksenberg, Jorge R; International MS Genetics Consortium
- 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 x 10(-11)), IRF8 (P = 3.73 x 10(-9)) and CD6 (P = 3.79 x 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.
- Publication
Nature genetics, 2009, Vol 41, Issue 7, p776
- ISSN
1546-1718
- Publication type
Journal Article
- DOI
10.1038/ng.401