Interleukin 7 receptor α chain (IL7R) shows allelic and functional association with multiple sclerosis

Simon G. Gregory, Silke Schmidt, Puneet Seth, Jorge R. Oksenberg, John Hart, Angela Prokop, Stacy J. Caillier, Maria Ban, An Goris, Lisa F. Barcellos, Robin Lincoln, Jacob L. McCauley, Stephen J. Sawcer, D. A.S. Compston, Benedicte Dubois, Stephen L. Hauser, Mariano A. Garcia-Blanco, Margaret A. Pericak-Vance, Jonathan L. Haines

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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 α chain (IL7R) as a significant risk factor for multiple sclerosis in four independent family-based or case-control data sets (overall P = 2.9 × 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.

Original languageEnglish (US)
Pages (from-to)1083-1091
Number of pages9
JournalNature Genetics
Volume39
Issue number9
DOIs
StatePublished - Sep 1 2007
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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    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., & Haines, J. L. (2007). Interleukin 7 receptor α chain (IL7R) shows allelic and functional association with multiple sclerosis. Nature Genetics, 39(9), 1083-1091. https://doi.org/10.1038/ng2103