Abstract
Genotyping of multiallelic copy number variants (CNVs) is technically difficult and can lead to inaccurate conclusions. This is reflected by inconsistent results published for the CNV C-C chemokine ligand 3-like 1 (CCL3L1) and its contribution to rheumatoid arthritis (RA) susceptibility. In order to draw robust conclusions about CCL3L1 involvement in RA, we have performed association analysis (CNVtools) using genotyping by the paralogue ratio test of a Norwegian RA case–control material (N=1877). We also analyzed the associations after stratification for anti-citrullinated peptide antibody (ACPA) status. Clear clusters representing specific copy number classes were evident, but significant differential bias was observed resulting in a systematic trend toward slightly higher apparent copy number for cases relative to controls. Controlling for bias revealed no significant differences in copy number distribution either between all patients and controls, or after ACPA stratification. Our results do not support involvement of the CCL3L1 CNV in RA susceptibility.
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Acknowledgements
We thank the Norwegian Bone Marrow Registry for making the control material available and Dr Stephen J Williams at the Fox Chase Cancer center, Philadelphia, USA for providing the OVCAR-5 reference sample. This work was supported by the Norwegian Research Council and Oslo University Hospital, by the South-Eastern Norway Regional Health Authority and by a Wellcome Trust grant awarded to JALA (number 083929).
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Nordang, G., Carpenter, D., Viken, M. et al. Association analysis of the CCL3L1 copy number locus by paralogue ratio test in Norwegian rheumatoid arthritis patients and healthy controls. Genes Immun 13, 579–582 (2012). https://doi.org/10.1038/gene.2012.30
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DOI: https://doi.org/10.1038/gene.2012.30
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