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The histone demethylase JARID1A is associated with susceptibility to ankylosing spondylitis

Genes & Immunity volume 12, pages 395–398 (2011)Cite this article

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Abstract

Associations with disease identified by genome-wide association studies (GWAS) must be replicated and refined to validate causative variants. In the Wellcome Trust Case Control Consortium (WTCCC) GWAS using 14 500 non-synonymous single nucleotide polymorphisms (nsSNP), rs11062385 (a nsSNP in JARID1A) showed nominal association with ankylosing spondylitis (AS) (P=0.0006, odds ratio (OR)=1.26, 95% confidence interval (95% CI)=1.1–1.4). To replicate and refine the association of JARID1A, rs11062385 was genotyped in 730 further cases and compared with allele frequencies in non-AS disease cohorts typed by WTCCC. We replicated the initial association (P=0.04, OR=1.16, 95% CI=1.01–1.34) and identified a strengthened association with AS in a meta-analysis of this new study combined with the original WTCCC study (P=0.0001, OR=1.21, 95% CI=1.10–1.33). We also genotyped nine further intronic tagging SNPs in JARID1A in 1604 AS cases and 1020 new control samples, but none was associated with AS. JARID1A or a locus in strong linkage disequilibrium with it is a positional candidate for susceptibility to AS.

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Acknowledgements

JP is funded by the NIHR Oxford Biomedical Research Centre ankylosing spondylitis chronic disease cohort (Theme Code: A91202). DH is funded by Arthritis Research UK (Grant no: 19356). CF is funded by the Thames Valley Comprehensive Local Research Network (TVCLRN), which forms part of the NIHR Comprehensive Clinical Research Network (CCRN). TK is funded by the Henni Mester studentship. This study was also funded, in part, by the Arthritis Research UK, award numbers 18797 and by the Wellcome Trust under award no. 076113. We are grateful to the many patients who contributed samples to these studies and to their physicians for allowing us to study their patients. We also thank the National Ankylosing Spondylitis Society (UK) for additional financial support for DH and their unstinting help in patient recruitment. We thank the Osteoarthritis Group, Oxford, for their control samples. This study makes use of data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the data is available at http://www.wtccc.org.uk. We acknowledge the use of genotype data from the British 1958 Birth Cohort DNA collection, funded by the Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02. Additional laboratory support was provided by the NIHR Oxford Musculoskeletal Biomedical Research Unit. Finally, we thank Lyn-Louise Johnson for iPLEX genotyping and the Bioinformatics and Statistical Genetics groups for support, both of the Wellcome Trust Centre for Human Genetics, Oxford.

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Authors and Affiliations

  1. National Institute for Health Research Oxford Musculoskeletal Biomedical Research Unit and Botnar Research Centre, Nuffield Orthopaedic Centre, Oxford, UK

    J J Pointon, D Harvey, T Karaderi, L H Appleton, C Farrar & B P Wordsworth

  2. National Institute for Health Research Oxford Comprehensive Biomedical Research Centre, Nuffield Orthopaedic Centre, Oxford, UK

    J J Pointon & B P Wordsworth

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  1. J J Pointon
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  2. D Harvey
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  3. T Karaderi
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Correspondence to J J Pointon.

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Pointon, J., Harvey, D., Karaderi, T. et al. The histone demethylase JARID1A is associated with susceptibility to ankylosing spondylitis. Genes Immun 12, 395–398 (2011). https://doi.org/10.1038/gene.2011.23

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