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Nature Genetics 39, 1083–1091 (1 September 2007) | doi:10.1038/ng2103

Interleukin 7 receptor |[alpha]| 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

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 |[times]| 10|[minus]|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.