REL, encoding a member of the NF-B family of transcription factors, is a newly defined risk locus for rheumatoid arthritis

Peter K. Gregersen, Chistopher I. Amos, Annette T. Lee, Yue Lu, Elaine F. Remmers, Daniel L. Kastner, Michael F Seldin, Lindsey A. Criswell, Robert M. Plenge, V. Michael Holers, Ted R. Mikuls, Tuulikki Sokka, Larry W. Moreland, S. Louis Bridges, Gang Xie, Ann B. Begovich, Katherine A. Siminovitch

Research output: Contribution to journalArticle

264 Scopus citations

Abstract

We conducted a genome-wide association study of rheumatoid arthritis in 2,418 cases and 4,504 controls from North America and identified an association at the REL locus, encoding c-Rel, on chromosome 2p13 (rs13031237, P = 6.01 × 10 10). Replication in independent case-control datasets comprising 2,604 cases and 2,882 controls confirmed this association, yielding an allelic OR = 1.25 (P = 3.08 × 10 14) for marker rs13031237 and an allelic OR = 1.21 (P = 2.60 × 10 11) for marker rs13017599 in the combined dataset. The combined dataset also provides definitive support for associations at both CTLA4 (rs231735; OR = 0.85; P = 6.25 × 10 9) and BLK (rs2736340; OR = 1.19; P = 5.69 × 10 9). c-Rel is an NF-B family member with distinct functional properties in hematopoietic cells, and its association with rheumatoid arthritis suggests disease pathways that involve other recently identified rheumatoid arthritis susceptibility genes including CD40, TRAF1, TNFAIP3 and PRKCQ.

Original languageEnglish (US)
Pages (from-to)820-823
Number of pages4
JournalNature Genetics
Volume41
Issue number7
DOIs
StatePublished - Jul 2009

ASJC Scopus subject areas

  • Genetics

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    Gregersen, P. K., Amos, C. I., Lee, A. T., Lu, Y., Remmers, E. F., Kastner, D. L., Seldin, M. F., Criswell, L. A., Plenge, R. M., Holers, V. M., Mikuls, T. R., Sokka, T., Moreland, L. W., Bridges, S. L., Xie, G., Begovich, A. B., & Siminovitch, K. A. (2009). REL, encoding a member of the NF-B family of transcription factors, is a newly defined risk locus for rheumatoid arthritis. Nature Genetics, 41(7), 820-823. https://doi.org/10.1038/ng.395