期刊
NATURE GENETICS
卷 45, 期 11, 页码 1353-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.2770
关键词
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资金
- US National Institutes of Health
- Wellcome Trust
- UK MS Society
- UK Medical Research Council
- US National MS Society
- Cambridge National Institute for Health Research (NIHR) Biomedical Research Centre
- DeNDRon
- Swedish Brain Foundation
- Swedish Research Council
- Knut and Alice Wallenberg Foundation
- Swedish Heart-Lung Foundation
- Foundation for Strategic Research
- MRC [G0800759, G0000934, G0600329, G0800675, G0700061] Funding Source: UKRI
- Chief Scientist Office [CZB/4/710, ETM/137] Funding Source: researchfish
- Crohn's and Colitis UK [M11-1] Funding Source: researchfish
- Medical Research Council [G0600329, G0800675, G0800759, G0801418B, G0700061, G0000934] Funding Source: researchfish
Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 x 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 x 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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