Interleukin 7 receptor α chain ( IL7R ) shows allelic and functional association with multiple sclerosis
Abstract
Multiple sclerosis is a demyelinating neurodegenerative disease with a strong genetic component. Previous genetic risk studies have failed to identify consistently linked regions or genes outside of the major histocompatibility complex on chromosome 6p. We describe allelic association of a polymorphism in the gene encoding the interleukin 7 receptor alpha chain (IL7R) as a significant risk factor for multiple sclerosis in four independent family-based or case-control data sets (overall P = 2.9 x 10(-7)). Further, the likely causal SNP, rs6897932, located within the alternatively spliced exon 6 of IL7R, has a functional effect on gene expression. The SNP influences the amount of soluble and membrane-bound isoforms of the protein by putatively disrupting an exonic splicing silencer.
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Linkage analyses in extended multiple sclerosis affected families validated the HLA association but showed no significant linkage to loci outside the MHC.
“These validated the HLA association but showed no significant linkage to loci outside the MHC.”
From Genome‐wide association studies of multiple sclerosis (2018) · cites this paper as [31]
The three significant findings from the first multiple sclerosis genome-wide association study were simultaneously replicated in independent studies from the United Kingdom, the United States and the Nordic countries.
“The three significant findings were simultaneously replicated in independent studies from the United Kingdom, the United States and the Nordic countries.31, 32”
From Genome‐wide association studies of multiple sclerosis (2018) · cites this paper as [31]
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- Authors
- for the Multiple Sclerosis Genetics Group, Gregory, S. G., Schmidt, S., Seth, P., Oksenberg, J. R., Hart, J., Prokop, A., Caillier, S. J., Ban, M., Goris, A., Barcellos, L. F., Lincoln, R., McCauley, J. L., Sawcer, S. J., Compston, D. A. S., Dubois, B., Hauser, S. L., Garcia-Blanco, M. A., & Pericak-Vance, M. A.
- Affiliations
- Duke University (US)
- University of California, San Francisco (US)
- University of Cambridge (GB)
- University of California, Berkeley (US)
- ORCID
- Venue
- Nature Genetics
- Published
- 2007-07-29
- Volume
- 39
- Issue
- 9
- Pages
- 1083-1091
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2171556560
- Cited by
- 657
- References
- 3
- Citations by year
- 2026: 12 · 2025: 14 · 2024: 16 · 2023: 11 · 2022: 22 · 2021: 24 · 2020: 21 · 2019: 23 · 2018: 24 · 2017: 30 · 2016: 25 · 2015: 33 · 2014: 38 · 2013: 49 · 2012: 49
- FWCI
- 49.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- multiple sclerosis, CD127, allelic association, genetic risk factors, alternative splicing, exonic splicing silencer, gene expression regulation, demyelinating disease
- MeSH terms
- Adult, Animals, Chromosome Mapping, Europe, Family Health, Female, Gene Frequency, Genotype, Haplotypes, HeLa Cells, Humans, Male, Middle Aged, Multiple Sclerosis, Transfection, United States, Linkage Disequilibrium, Gene Expression, Odds Ratio, Case-Control Studies, Alternative Splicing, Genetic Predisposition to Disease, Receptors, Interleukin-7, Polymorphism, Single Nucleotide, Cell Line, Tumor
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