|Publication Type||Journal Article|
|Year of Publication||2007|
|Authors||Hafler, 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 Authors||International Multiple Sclerosis Genetics Consortium|
|Journal||N Engl J Med|
|Date Published||2007 Aug 30|
|Keywords||Adolescent, 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|
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.
|Alternate Journal||N. Engl. J. Med.|
|Grant List||R01 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