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N Engl J Med DOI:10.1056/NEJMoa073493

Risk alleles for multiple sclerosis identified by a genomewide study.

Publication TypeJournal Article
Year of Publication2007
AuthorsHafler, DA, Compston, A, Sawcer, S, Lander, ES, Daly, MJ, De Jager, PL, de Bakker, PIW, Gabriel, SB, Mirel, DB, Ivinson, AJ, Pericak-Vance, MA, Gregory, SG, Rioux, JD, McCauley, JL, Haines, JL, Barcellos, LF, Cree, B, Oksenberg, JR, Hauser, SL
Corporate AuthorsInternational Multiple Sclerosis Genetics Consortium
JournalN Engl J Med
Volume357
Issue9
Pages851-62
Date Published2007 Aug 30
ISSN1533-4406
KeywordsAdolescent, Adult, Aged, Alleles, Female, Genetic Predisposition to Disease, Genome, Human, HLA-DR alpha-Chains, HLA-DR Antigens, Humans, Interleukin-2 Receptor alpha Subunit, Interleukin-7 Receptor alpha Subunit, Linkage Disequilibrium, Male, Middle Aged, Multiple Sclerosis, Mutation, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Risk Factors
Abstract

BACKGROUND: Multiple sclerosis has a clinically significant heritable component. We conducted a genomewide association study to identify alleles associated with the risk of multiple sclerosis.

METHODS: We used DNA microarray technology to identify common DNA sequence variants in 931 family trios (consisting of an affected child and both parents) and tested them for association. For replication, we genotyped another 609 family trios, 2322 case subjects, and 789 control subjects and used genotyping data from two external control data sets. A joint analysis of data from 12,360 subjects was performed to estimate the overall significance and effect size of associations between alleles and the risk of multiple sclerosis.

RESULTS: A transmission disequilibrium test of 334,923 single-nucleotide polymorphisms (SNPs) in 931 family trios revealed 49 SNPs having an association with multiple sclerosis (P

CONCLUSIONS: Alleles of IL2RA and IL7RA and those in the HLA locus are identified as heritable risk factors for multiple sclerosis.

URLhttp://dx.doi.org/10.1056/NEJMoa073493
DOI10.1056/NEJMoa073493
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/17660530?dopt=Abstract

Alternate JournalN. Engl. J. Med.
PubMed ID17660530
Grant ListR01 NS049477 / NS / NINDS NIH HHS / United States
AI067152 / AI / NIAID NIH HHS / United States
076113 / / Wellcome Trust / United Kingdom
NS2427 / NS / NINDS NIH HHS / United States
P01-AI039671 / AI / NIAID NIH HHS / United States
NS26799 / NS / NINDS NIH HHS / United States
U54-RR020278-1 / RR / NCRR NIH HHS / United States
NS032830 / NS / NINDS NIH HHS / United States
NS049477 / NS / NINDS NIH HHS / United States
U19 AI067152 / AI / NIAID NIH HHS / United States