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A candidate gene study of CLEC16A does not provide evidence of association with risk for anti-CCP-positive rheumatoid arthritis

Abstract

CLEC16A, a putative immunoreceptor, was recently established as a susceptibility locus for type I diabetes and multiple sclerosis. Subsequently, associations between CLEC16A and rheumatoid arthritis (RA), Addison's disease and Crohn's disease have been reported. A large comprehensive and independent investigation of CLEC16A variation in RA was pursued. This study tested 251 CLEC16A single-nucleotide polymorphisms in 2542 RA cases (85% anti-cyclic citrullinated peptide (anti-CCP) positive) and 2210 controls (N=4752). All individuals were of European ancestry, as determined by ancestry informative genetic markers. No evidence for significant association between CLEC16A variation and RA was observed. This is the first study to fully characterize common genetic variation in CLEC16A including assessment of haplotypes and gender-specific effects. The previously reported association between RA and rs6498169 was not replicated. Results show that CLEC16A does not have a prominent function in susceptibility to anti-CCP-positive RA.

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Acknowledgements

We thank Farren BS Briggs, Benjamin A Goldstein, Alan Hubbard and Ira Tager for helpful discussion, as well as study participants. This work was supported by an Abbott Graduate Student Achievement Award (ACR REF), Grants R01 AI065841, R01 AI059829 and F31 AI075609 (NIH/NIAID), and Grants RO1 AR44422, NO1 AR22263, R01 AR050267 and K24 AR02175 (NIH/NIAMS). The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, NIAID or NIAMS. This study makes use of data generated by the WTCCC; a full list of the investigators who contributed to the generation of the data is available at www.wtccc.org.uk, and funding for the project was provided by the Wellcome Trust under award 076113. These studies were performed in part in the General Clinical Research Center, Moffitt Hospital, University of California, San Francisco, with funds provided by the National Center for Research Resources, 5 M01 RR-00079, US Public Health Service.

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Correspondence to L F Barcellos.

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Bronson, P., Ramsay, P., Seldin, M. et al. A candidate gene study of CLEC16A does not provide evidence of association with risk for anti-CCP-positive rheumatoid arthritis. Genes Immun 11, 504–508 (2010). https://doi.org/10.1038/gene.2010.7

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