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

D. L. Armstrong, A. Reiff, B. L. Myones, F. P. Quismorio, M. Klein-Gitelman, D. McCurdy, L. Wagner-Weiner, E. Silverman, J. O. Ojwang, K. M. Kaufman, J. A. Kelly, J. T. Merrill, J. B. Harley, S. C. Bae, T. J. Vyse, G. S. Gilkeson, P. M. Gaffney, K. L. Moser, Chaim Putterman, J. C. EdbergE. E. Brown, J. Ziegler, C. D. Langefeld, R. Zidovetzki, C. O. Jacob

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

In our earlier study, we utilized a Bayesian design to probe the association of ∼1000 genes (∼10000 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.

Original languageEnglish (US)
Pages (from-to)446-456
Number of pages11
JournalGenes and Immunity
Volume10
Issue number5
DOIs
StatePublished - 2009

Fingerprint

Systemic Lupus Erythematosus
Genes
Single Nucleotide Polymorphism
Class 2 Receptor-Like Protein Tyrosine Phosphatases
Toll-Like Receptor 8
Interleukin-16
Population Control
Parents

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Cite this

Armstrong, D. L., Reiff, A., Myones, B. L., Quismorio, F. P., Klein-Gitelman, M., McCurdy, D., ... Jacob, C. O. (2009). Identification of new SLE-associated genes with a two-step Bayesian study design. Genes and Immunity, 10(5), 446-456. https://doi.org/10.1038/gene.2009.38

Identification of new SLE-associated genes with a two-step Bayesian study design. / Armstrong, D. L.; Reiff, A.; Myones, B. L.; Quismorio, F. P.; Klein-Gitelman, M.; McCurdy, D.; Wagner-Weiner, L.; Silverman, E.; Ojwang, J. O.; Kaufman, K. M.; Kelly, J. A.; Merrill, J. T.; Harley, J. B.; Bae, S. C.; Vyse, T. J.; Gilkeson, G. S.; Gaffney, P. M.; Moser, K. L.; Putterman, Chaim; Edberg, J. C.; Brown, E. E.; Ziegler, J.; Langefeld, C. D.; Zidovetzki, R.; Jacob, C. O.

In: Genes and Immunity, Vol. 10, No. 5, 2009, p. 446-456.

Research output: Contribution to journalArticle

Armstrong, DL, Reiff, A, Myones, BL, Quismorio, FP, Klein-Gitelman, M, McCurdy, D, Wagner-Weiner, L, Silverman, E, Ojwang, JO, Kaufman, KM, Kelly, JA, Merrill, JT, Harley, JB, Bae, SC, Vyse, TJ, Gilkeson, GS, Gaffney, PM, Moser, KL, Putterman, C, Edberg, JC, Brown, EE, Ziegler, J, Langefeld, CD, Zidovetzki, R & Jacob, CO 2009, 'Identification of new SLE-associated genes with a two-step Bayesian study design', Genes and Immunity, vol. 10, no. 5, pp. 446-456. https://doi.org/10.1038/gene.2009.38
Armstrong DL, Reiff A, Myones BL, Quismorio FP, Klein-Gitelman M, McCurdy D et al. Identification of new SLE-associated genes with a two-step Bayesian study design. Genes and Immunity. 2009;10(5):446-456. https://doi.org/10.1038/gene.2009.38
Armstrong, D. L. ; Reiff, A. ; Myones, B. L. ; Quismorio, F. P. ; Klein-Gitelman, M. ; McCurdy, D. ; Wagner-Weiner, L. ; Silverman, E. ; Ojwang, J. O. ; Kaufman, K. M. ; Kelly, J. A. ; Merrill, J. T. ; Harley, J. B. ; Bae, S. C. ; Vyse, T. J. ; Gilkeson, G. S. ; Gaffney, P. M. ; Moser, K. L. ; Putterman, Chaim ; Edberg, J. C. ; Brown, E. E. ; Ziegler, J. ; Langefeld, C. D. ; Zidovetzki, R. ; Jacob, C. O. / Identification of new SLE-associated genes with a two-step Bayesian study design. In: Genes and Immunity. 2009 ; Vol. 10, No. 5. pp. 446-456.
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AU - Moser, K. L.

AU - Putterman, Chaim

AU - Edberg, J. C.

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