期刊
NATURE GENETICS
卷 41, 期 7, 页码 776-U26出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.401
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资金
- Medical Research Council [G0000934, MC_QA137934] Funding Source: Medline
- NIAID NIH HHS [P01 AI039671] Funding Source: Medline
- NIAMS NIH HHS [K08 AR055688-01A1, K08 AR055688] Funding Source: Medline
- NINDS NIH HHS [R01 NS046630, K08 NS046341, R01 NS049477, K08 NS46341] Funding Source: Medline
- Wellcome Trust [068545/Z/02] Funding Source: Medline
- MRC [G0000934, MC_qA137934] Funding Source: UKRI
- Medical Research Council [G0000934, MC_qA137934] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0508-10335] Funding Source: researchfish
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.
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