@article{b3f8e77e9a5245c98dd61c55e9df96c9,
title = "Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci",
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.",
author = "{De Jager}, {Philip L.} and Xiaoming Jia and Joanne Wang and {De Bakker}, {Paul I.W.} and Linda Ottoboni and Aggarwal, {Neelum T.} and Laura Piccio and Soumya Raychaudhuri and Dong Tran and Cristin Aubin and Rebeccah Briskin and Susan Romano and Baranzini, {Sergio E.} and McCauley, {Jacob L.} and Pericak-Vance, {Margaret A.} and Haines, {Jonathan L.} and Gibson, {Rachel A.} and Yvonne Naeglin and Bernard Uitdehaag and Matthews, {Paul M.} and Ludwig Kappos and Chris Polman and McArdle, {Wendy L.} and Strachan, {David P.} and Denis Evans and Cross, {Anne H.} and Daly, {Mark J.} and Alastair Compston and Sawcer, {Stephen J.} and Weiner, {Howard L.} and Hauser, {Stephen L.} and Hafler, {David A.} and Oksenberg, {Jorge R.}",
note = "Funding Information: P.L.D. is a Harry Weaver Neuroscience Scholar Award of the National MS Society (NMSS); he is also a William C. Fowler Scholar in Multiple Sclerosis Research and is supported by a National Institute of Neurological Disorders and Stroke (NINDS) K08 grant, NS46341. D.A.H. is a Jacob Javits Scholar of the US National Institutes of Health; he is also supported by NINDS P01 AI039671, R01 NS049477, R01NS046630, NMSS Collaborative MS Research Award and NMSS RG3567A. The International MS Genetics Consortium is supported by R01NS049477. L.P. is supported by an NMSS fellowship grant (FG1665-A-1). The genome-wide data on the BWH subjects and the RNA data on MS and CIS subjects from the CLIMB study were generated as part of a collaboration with Affymetrix, Inc. We thank the Myocardial Infarction Genetics Consortium (MIGen) study for the use of their genotype data as control data in our study. The MIGen study was funded by the US National Institutes of Health and National Heart, Lung, and Blood Institute{\textquoteright}s STAMPEED genomics research program and a grant from the National Center for Research Resources. We acknowledge use of genotype data from the British 1958 Birth Cohort DNA collection, funded by the Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02. We thank R. Lincoln and R. Gomez for expert specimen management at UCSF as well as A. Santaniello for database management. We thank the Accelerated Cure Project for its work in collecting samples from subjects with MS and for making these samples available to MS investigators. We also thank the following clinicians for contributing to sample collection efforts: Accelerated Cure project, E. Frohman, B. Greenberg, P. Riskind, S. Sadiq, B. Thrower and T. Vollmer; Washington University, B.J. Parks and R.T. Naismith. Finally, we thank the Brigham & Women{\textquoteright}s Hospital PhenoGenetic Project for providing DNA samples from healthy subjects that were used in the replication effort of this study.",
year = "2009",
month = jul,
doi = "10.1038/ng.401",
language = "English",
volume = "41",
pages = "776--782",
journal = "Nature Genetics",
issn = "1061-4036",
number = "7",
}