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The association of PTPN22 rs2476601 with juvenile idiopathic arthritis is specific to females

Genes & Immunity volume 16, pages 495–498 (2015)Cite this article

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Abstract

A preponderance of females develop autoimmune disease, including juvenile idiopathic arthritis (JIA), yet the reason for this bias remains elusive. Evidence suggests that genetic risk of disease may be influenced by sex. PTPN22 rs2476601 is associated with JIA and numerous other autoimmune diseases, and has been reported to show female-specific association with type 1 diabetes. We performed main effect and sex-stratified association analyses to determine whether a sex-specific association exists in JIA. As expected, rs2476601 was associated with JIA in our discovery (413 cases and 690 controls) and replication (1008 cases and 9284 controls) samples. Discovery sample sex-stratified analyses demonstrated an association specifically in females (odds ratio (OR)=2.35, 95% confidence interval (CI)=1.52-3.63, P=0.00011) but not males (OR=0.91, 95% CI=0.52–1.60, P=0.75). This was similarly observed in the replication sample. There was evidence for genotype-by-sex interaction (Pinteraction=0.009). The association between rs2476601 and JIA appears restricted to females, partly accounting for the predominance of females with this disease.

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Acknowledgements

We thank the participants and their families for their generous donation of information and biospecimens to this study, along with the research staff who recruited them. We acknowledge funding from the National Health and Medical Research Council of Australia (NHMRC, #APP1026349), along with a number of other philanthropic organizations including Arthritis Australia, Australian Academy of Science (Travelling Fellowship to the USA to JAE) and the Rebecca Cooper Foundation. This work was supported by the Victorian State Government Operational Infrastructure Program; and by The Children’s Hospital of Philadelphia Research Institute, the Moran Family Foundation and the National Institutes of Health (RC1 AR058606) to HH and THF. JAE is supported by an Australian Research Council Future Fellowship (#FT120100253). YRL is supported by the Paul and Daisy Soros Fellowship for New Americans and the NIH Medical Scientist Training Program. ALP and RS are supported by National Health and Medical Research Council (Australia) Senior Research Fellowships.

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Authors and Affiliations

  1. Genes, Environment and Complex Disease, Murdoch Childrens Research Institute, Parkville, Victoria, Australia

    R C Chiaroni-Clarke, R A Chavez & J A Ellis

  2. Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia

    R C Chiaroni-Clarke, R A Chavez, R Saffery, A-L Ponsonby & J A Ellis

  3. Medical Scientist Training Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Y R Li

  4. Department of Pediatrics, Center for Applied Genomics, Abramson Research Center, Children's Hospital of Philadelphia, Philadelphia, PA, USA

    Y R Li & H Hakonarson

  5. Paediatric Rheumatology Unit, Royal Children’s Hospital, Parkville, Victoria, Australia

    J E Munro, J D Akikusa & R C Allen

  6. Arthritis and Rheumatology Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia

    J E Munro, J D Akikusa & R C Allen

  7. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, Victoria, Australia

    K J Scurrah

  8. Environmental and Genetic Epidemiology Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia

    A Pezic & A-L Ponsonby

  9. Department of Paediatric Rheumatology, Monash Children’s Hospital, Monash Medical Centre, Clayton, Victoria, Australia

    S E Piper

  10. Division of Rheumatology and Clinical Pharmacology, Medical Toxicology and Therapeutic Innovation, Children’s Mercy Kansas City, Kansas City, MO, USA

    M L Becker

  11. Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    S D Thompson

  12. Department of Immunology, Oslo University Hospital and University of Oslo, Oslo, Norway

    B A Lie

  13. Department of Rheumatology, Oslo University Hospital, Oslo, Norway

    B Flato & O Forre

  14. Pediatric Rheumatology, Texas Scottish Rite Hospital for Children, Dallas, TX, USA

    M Punaro

  15. Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Texas Scottish Rite Hospital for Children, Dallas, TX, USA

    C Wise

  16. Cancer and Disease Epigenetics, Murdoch Childrens Research Institute, Parkville, Victoria, Australia

    R Saffery

  17. Department of Pediatrics, Nemours Children’s Hospital, Orlando, FL, USA

    T H Finkel

  18. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    T H Finkel & H Hakonarson

Authors
  1. R C Chiaroni-Clarke
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  2. Y R Li
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  3. J E Munro
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  4. R A Chavez
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  5. K J Scurrah
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  6. A Pezic
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  7. J D Akikusa
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  8. R C Allen
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  9. S E Piper
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  10. M L Becker
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  11. S D Thompson
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  12. B A Lie
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  13. B Flato
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  14. O Forre
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  15. M Punaro
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  16. C Wise
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  17. R Saffery
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  18. T H Finkel
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  19. H Hakonarson
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  20. A-L Ponsonby
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  21. J A Ellis
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Corresponding author

Correspondence to J A Ellis.

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Chiaroni-Clarke, R., Li, Y., Munro, J. et al. The association of PTPN22 rs2476601 with juvenile idiopathic arthritis is specific to females. Genes Immun 16, 495–498 (2015). https://doi.org/10.1038/gene.2015.32

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  • DOI: https://doi.org/10.1038/gene.2015.32

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