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

doi:10.1038/ng2103

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 language	English (US)
Pages (from-to)	1083-1091
Number of pages	9
Journal	Nature Genetics
Volume	39
Issue number	9
DOIs	https://doi.org/10.1038/ng2103
State	Published - Sep 2007
Externally published	Yes

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

Gregory, SG, Schmidt, S, Seth, P, Oksenberg, JR, Hart, J, Prokop, A, Caillier, SJ, Ban, M, Goris, A, Barcellos, LF, Lincoln, R, McCauley, JL, Sawcer, SJ, Compston, DAS, Dubois, B, Hauser, SL, Garcia-Blanco, MA, Pericak-Vance, MA & Haines, JL 2007, 'Interleukin 7 receptor α chain (IL7R) shows allelic and functional association with multiple sclerosis', Nature Genetics, vol. 39, no. 9, pp. 1083-1091. https://doi.org/10.1038/ng2103

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title = "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 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.",

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

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AU - Prokop, Angela

AU - Caillier, Stacy J.

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AU - Goris, An

AU - Barcellos, Lisa F.

AU - Lincoln, Robin

AU - McCauley, Jacob L.

AU - Sawcer, Stephen J.

AU - Compston, D. A.S.

AU - Dubois, Benedicte

AU - Hauser, Stephen L.

AU - Garcia-Blanco, Mariano A.

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AU - Haines, Jonathan L.

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AB - 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.

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

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