The authors wish it to be known that the last two authors should be regarded as joint last authors.
Confirmation of association of FCGR3B but not FCGR3A copy number with susceptibility to autoantibody positive rheumatoid arthritis†
Article first published online: 28 FEB 2012
© 2012 Wiley Periodicals, Inc.
Special Issue: Focus on the NIH Undiagnosed Diseases Program
Volume 33, Issue 4, pages 741–749, April 2012
How to Cite
Robinson, J. I., Carr, I. M., Cooper, D. L., Rashid, L. H., Martin, S. G., Emery, P., Isaacs, J. D., Barton, A., BRAGGSS, Wilson, A. G., Barrett, J. H. and Morgan, A. W. (2012), Confirmation of association of FCGR3B but not FCGR3A copy number with susceptibility to autoantibody positive rheumatoid arthritis. Hum. Mutat., 33: 741–749. doi: 10.1002/humu.22031
Communicated by Christopher Mathew
- Issue published online: 12 MAR 2012
- Article first published online: 28 FEB 2012
- Accepted manuscript online: 30 JAN 2012 12:00AM EST
- Manuscript Accepted: 17 JAN 2012
- Manuscript Received: 18 OCT 2011
- Arthritis Research UK. Grant Number: 13569 and 18066
- rheumatoid arthritis;
The FCGR locus encoding the low-affinity Fcγ receptors (FcγR) for immunoglobulin G has largely been missed by genome-wide association studies due to complications with structural variation and segmental duplication. Recently identified copy number variants (CNVs) affecting FCGR3A and FCGR3B have been linked to a number of autoimmune disorders. We have developed and validated a novel quantitative sequence variant assay in combination with an adapted paralogue ratio test to examine independent CNVs carrying FCGR3A and FCGR3B in rheumatoid arthritis (RA) compared with healthy volunteers (n = 1,115 and 654, respectively). Implementation of a robust statistical analysis framework (CNVtools) allowed for systematic batch effects and for the inherent uncertainty of copy number assignment, thus avoiding two major sources of false positive results. Evidence for association with neither duplications nor deletions of FCGR3A was found; however, in line with previous studies, there was evidence of overrepresentation of FCGR3B deletions in RA (odds ratio [OR] 1.50, P = 0.028), which was more apparent in rheumatoid factor positive disease (OR 1.61, P = 0.011). The level of FcγRIIIb, encoded by FCGR3B, expression on neutrophils was shown to correlate with gene copy number. Thus, our results may highlight an important role for neutrophils in the pathogenesis of RA, potentially through reduced FcγRIIIb-mediated immune complex clearance. Hum Mutat 33:741–749, 2012. © 2012 Wiley Periodicals, Inc.