@article{ff0e67216c9e40e39ab888cea1755965,
title = "Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk",
abstract = "To discover new rheumatoid arthritis (RA) risk loci, we systematically examined 370 SNPs from 179 independent loci with P <0.001 in a published meta-analysis of RA genome-wide association studies (GWAS) of 3,393 cases and 12,462 controls. We used Gene Relationships Across Implicated Loci (GRAIL), 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. 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 were convincingly validated: CD2-CD58 (rs11586238, P = 1 x 10(-6) replication, P = 1 x 10(-9) overall), CD28 (rs1980422, P = 5 x 10(-6) replication, P = 1 x 10(-9) overall) and PRDM1 (rs548234, P = 1 x 10(-5) replication, P = 2 x 10(-8) overall). An additional four were replicated (P <0.0023): TAGAP (rs394581, P = 0.0002 replication, P = 4 x 10(-7) overall), PTPRC (rs10919563, P = 0.0003 replication, P = 7 x 10(-7) overall), TRAF6-RAG1 (rs540386, P = 0.0008 replication, P = 4 x 10(-6) overall) and FCGR2A (rs12746613, P = 0.0022 replication, P = 2 x 10(-5) overall). Many of these loci are also associated to other immunologic diseases.",
keywords = "antigens, CD2, antigens, CD28, antigens, CD58, arthritis, rheumatoid, case-control studies, genetic predisposition to disease, genetic Variation, genotype, humans, polymorphism, single nucleotide, repressor proteins, risk factors",
author = "Soumya Raychaudhuri and Thomson, {Brian P} and Remmers, {Elaine F} and Stephen Eyre and Anne Hinks and Candace Guiducci and Catanese, {Joseph J} and Gang Xie and Stahl, {Eli A} and Robert Chen and Lars Alfredsson and Amos, {Christopher I} and Ardlie, {Kristin G} and Anne Barton and John Bowes and Burtt, {Noel P} and Monica Chang and Jonathan Coblyn and Costenbader, {Karen H} and Criswell, {Lindsey A} and Crusius, {J Bart A} and Jing Cui and {De Jager}, {Phillip L} and Bo Ding and Paul Emery and Edward Flynn and Pille Harrison and Lynne Hocking and Huizinga, {Tom W J} and Kastner, {Daniel L} and Xiayi Ke and Kurreeman, {Fina A S} and Lee, {Annette T} and Xiangdong Liu and Yonghong Li and Paul Martin and Morgan, {Ann W} and Leonid Padyukov and Reid, {David M} and Mark Seielstad and Seldin, {Michael F} and Shadick, {Nancy A} and Sophia Steer and Tak, {Paul P} and Wendy Thomson and {van der Helm-van Mil}, {Annette H M} and {van der Horst-Bruinsma}, {Irene E} and Weinblatt, {Michael E} and Wilson, {Anthony G} and Wolbink, {Gert Jan} and {BIRAC consortium}",
year = "2009",
month = dec,
doi = "10.1038/ng.479",
language = "English",
volume = "41",
pages = "1313--1318",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "12",
}