Genetic variants at CD28, PRDM1, and CD2/CD58 are associated with rheumatoid arthritis risk

To discover novel RA risk loci, we systematically examined 370 SNPs from 179 independent loci with p<0.001 in a published meta-analysis of RA GWAS of 3,393 cases and 12,462 controls(1). We used GRAIL(2), a computational method that applies statistical text mining to PubMed abstracts, to score the...

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Detalles Bibliográficos
Autores principales: Raychaudhuri, Soumya, Thomson, Brian P., Remmers, Elaine F., Eyre, Stephen, Hinks, Anne, Guiducci, Candace, Catanese, Joseph J., Xie, Gang, Stahl, Eli A., Chen, Robert, Alfredsson, Lars, Amos, Christopher I., Ardlie, Kristin G., Barton, Anne, Bowes, John, Burtt, Noel P., Chang, Monica, Coblyn, Jonathan, Costenbader, Karen H., Criswell, Lindsey A., Crusius, J. Bart A., Cui, Jing, De Jager, Phillip L., Ding, Bo, Emery, Paul, Flynn, Edward, Harrison, Pille, Hocking, Lynne J., Huizinga, Tom W. J., Kastner, Daniel L., Ke, Xiayi, Kurreeman, Fina A. S., Lee, Annette T., Liu, Xiangdong, Li, Yonghong, Martin, Paul, Morgan, Ann W., Padyukov, Leonid, Reid, David M., Seielstad, Mark, Seldin, Michael F., Shadick, Nancy A., Steer, Sophia, Tak, Paul P., Thomson, Wendy, van der Helm-van Mil, Annette H. M., van der Horst-Bruinsma, Irene E., Weinblatt, Michael E., Wilson, Anthony G., Wolbink, Gert Jan, Wordsworth, Paul, Altshuler, David, Karlson, Elizabeth W., Toes, Rene E. M., de Vries, Niek, Begovich, Ann B., Siminovitch, Katherine A., Worthington, Jane, Klareskog, Lars, Gregersen, Peter K., Daly, Mark J., Plenge, Robert M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2009
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142887/
https://www.ncbi.nlm.nih.gov/pubmed/19898481
http://dx.doi.org/10.1038/ng.479
Descripción
Sumario:To discover novel RA risk loci, we systematically examined 370 SNPs from 179 independent loci with p<0.001 in a published meta-analysis of RA GWAS of 3,393 cases and 12,462 controls(1). We used GRAIL(2), a computational method that applies statistical text mining to PubMed abstracts, to score these 179 loci for functional relationships to genes in 16 established RA disease loci(1,3-11). We identified 22 loci with a significant degree of functional connectivity. We genotyped 22 representative SNPs in an independent set of 7,957 cases and 11,958 matched controls. Three validate convincingly: CD2/CD58 (rs11586238, p=1×10(−6) replication, p=1×10(−9) overall), and CD28 (rs1980422, p=5×10(−6) replication, p=1×10(−9) overall), PRDM1 (rs548234, p=1×10(−5) replication, p=2×10(−8) overall). An additional four replicate (p<0.0023): TAGAP (rs394581, p=0.0002 replication, p=4×10(−7) overall), PTPRC (rs10919563, p=0.0003 replication, p=7×10(−7) overall), TRAF6/RAG1 (rs540386, p=0.0008 replication, p=4×10(−6) overall), and FCGR2A (rs12746613, p=0.0022 replication, p=2×10(−5) overall). Many of these loci are also associated to other immunologic diseases.

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