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Identification of new SLE-associated genes with a two-step Bayesian study design

Genes & Immunity volume 10, pages 446–456 (2009)Cite this article

Abstract

In our earlier study, we utilized a Bayesian design to probe the association of ∼1000 genes (∼10 000 single-nucleotide polymorphisms (SNPs)) with systemic lupus erythematosus (SLE) on a moderate number of trios of parents and children with SLE. Two genes associated with SLE, with a multitest-corrected false discovery rate (FDR) of <0.05, were identified, and a number of noteworthy genes with FDR of <0.8 were also found, pointing out a future direction for the study. In this report, using a large population of controls and adult- or childhood-onset SLE cases, we have extended the earlier investigation to explore the SLE association of 10 of these noteworthy genes (109 SNPs). We have found that seven of these genes exhibit a significant (FDR<0.05) association with SLE, both confirming some genes that have earlier been found to be associated with SLE (PTPN22 and IRF5) and presenting novel findings of genes (KLRG1, interleukin-16, protein tyrosine phosphatase receptor type T, toll-like receptor (TLR)8 and CASP10), which have not been reported earlier. The results signify that the two-step candidate pathway design is an efficient way to study the genetic foundations of complex diseases. Furthermore, the novel genes identified in this study point to new directions in both the diagnosis and the eventual treatment of this debilitating disease.

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Acknowledgements

This work was supported in part by NIH Grant RO1AR445650 to COJ and ALR, Grant 52104 to COJ and RZ. Work at OMRF was supported by National Institutes of Health (AI063622, RR020143, AR053483, AR049084, AI24717, AR42460, AR048940, AR445650 and AR043274), the Alliance for Lupus Research and the US Department of Veterans Affairs. The work at UAB was supported by NIH grants P01-AR49084 and P60-AR48095, SCB was supported by the Ministry for Health, Welfare and Family Affairs, Republic of Korea grants A010252 and A080588.

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Authors and Affiliations

  1. Department of Medicine, The Lupus Genetic Group, University of Southern California, Los Angeles, CA, USA

    D L Armstrong, A Reiff, F P Quismorio Jr & C O Jacob

  2. Department of Cell Biology and Neuroscience, University of California, Riverside, CA, USA

    D L Armstrong & R Zidovetzki

  3. Childrens Hospital of Los Angeles, Los Angeles, CA, USA

    A Reiff

  4. Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA

    B L Myones

  5. Children's Memorial Hospital and Northwestern University, Chicago, IL, USA

    M Klein-Gitelman

  6. Department of Pediatrics, UCLA, Los Angeles, CA, USA

    D McCurdy

  7. LaRabida Hospital and University of Chicago, Chicago, IL, USA

    L Wagner-Weiner

  8. Hospital for Sick Children, Toronto, Ontario, Canada

    E Silverman

  9. Oklahoma Medical Research Foundation, Oklahoma City, OK, USA

    J O Ojwang, K M Kaufman, J A Kelly, J T Merrill, J B Harley, P M Gaffney & K L Moser

  10. Department of Rheumatology, the Hospital for Rheumatic Diseases, Hanyang University, Seoul, Republic of Korea

    S-C Bae

  11. Imperial College London, Hammersmith Hospital, London, UK

    T J Vyse

  12. Medical University of South Carolina, Charleston, SC, USA

    G S Gilkeson

  13. Division of Rheumatology, Albert Einstein College of Medicine, Bronx, NY, USA

    C Putterman

  14. Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama, Birmingham, AL, USA

    J C Edberg & E E Brown

  15. Wake Forest University Health Sciences, Winston-Salem, NC, USA

    J Ziegler & C D Langefeld

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  1. D L Armstrong
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Correspondence to R Zidovetzki or C O Jacob.

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Armstrong, D., Reiff, A., Myones, B. et al. Identification of new SLE-associated genes with a two-step Bayesian study design. Genes Immun 10, 446–456 (2009). https://doi.org/10.1038/gene.2009.38

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