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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

New susceptibility locus for rheumatoid arthritis suggested by a genome-wide linkage study.

Rheumatoid arthritis (RA), the most common autoimmune disease, is associated in families with other autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM). Its genetic component has been suggested by familial aggregation (lambdas = 5), twin studies, and segregation analysis. HLA, which is the only susceptibility locus known, has been estimated to account for one-third of this component. The aim of this paper was to identify new RA loci. A genome scan was performed with 114 European Caucasian RA sib pairs from 97 nuclear families. Linkage was significant only for HLA (P < 2.5.10(-5)) and nominal for 19 markers in 14 other regions (P < 0.05). Four of the loci implicated in IDDM potentially overlap with these regions: the putative IDDM6, IDDM9, IDDM13, and DXS998 loci. The first two of these candidate regions, defined in the RA genome scan by the markers D18S68-D18S61-D18S469 (18q22-23) and D3S1267 (3q13), respectively, were studied in 194 additional RA sib pairs from 164 nuclear families. Support for linkage to chromosome 3 only was extended significantly (P = 0.002). The analysis of all 261 families provided a linkage evidence of P = 0. 001 and suggested an interaction between this putative RA locus and HLA. This locus could account for 16% of the genetic component of RA. Candidate genes include those coding for CD80 and CD86, molecules involved in antigen-specific T cell recognition. In conclusion, this first genome scan in RA Caucasian families revealed 14 candidate regions, one of which was supported further by the study of a second set of families.[1]


  1. New susceptibility locus for rheumatoid arthritis suggested by a genome-wide linkage study. Cornélis, F., Fauré, S., Martinez, M., Prud'homme, J.F., Fritz, P., Dib, C., Alves, H., Barrera, P., de Vries, N., Balsa, A., Pascual-Salcedo, D., Maenaut, K., Westhovens, R., Migliorini, P., Tran, T.H., Delaye, A., Prince, N., Lefevre, C., Thomas, G., Poirier, M., Soubigou, S., Alibert, O., Lasbleiz, S., Fouix, S., Bouchier, C., Lioté, F., Loste, M.N., Lepage, V., Charron, D., Gyapay, G., Lopes-Vaz, A., Kuntz, D., Bardin, T., Weissenbach, J. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
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