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; C. Putterman; J. C. Edberg; E. E. Brown; J. Ziegler; C. D. Langefeld; R. Zidovetzki; C. O. Jacob

doi:10.1038/gene.2009.38

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, C. Putterman, J. C. EdbergE. E. Brown, J. Ziegler, C. D. Langefeld, R. Zidovetzki, C. O. Jacob

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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 language	English
Pages (from-to)	446-456
Number of pages	11
Journal	Genes and Immunity
Volume	10
Issue number	5
DOIs	https://doi.org/10.1038/gene.2009.38
State	Published - Jul 2009
Externally published	Yes

Bibliographical note

Funding Information:
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.

Funding

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.

Funders	Funder number
Ministry for Health, Welfare and Family Affairs, Republic of Korea	A010252, A080588
National Institutes of Health	RO1AR445650, AR053483, AR043274, AR048940, AR42460, 52104, AI24717, AI063622, RR020143
National Institute of Arthritis and Musculoskeletal and Skin Diseases	P01AR049084
U.S. Department of Veterans Affairs	P60-AR48095, P01-AR49084
Alliance for Lupus Research

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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, C., ... 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

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title = "Identification of new SLE-associated genes with a two-step Bayesian study design",

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.",

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

note = "Funding Information: 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.",

year = "2009",

month = jul,

doi = "10.1038/gene.2009.38",

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journal = "Genes and Immunity",

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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

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T1 - Identification of new SLE-associated genes with a two-step Bayesian study design

AU - Armstrong, D. L.

AU - Reiff, A.

AU - Myones, B. L.

AU - Quismorio, F. P.

AU - Klein-Gitelman, M.

AU - McCurdy, D.

AU - Wagner-Weiner, L.

AU - Silverman, E.

AU - Ojwang, J. O.

AU - Kaufman, K. M.

AU - Kelly, J. A.

AU - Merrill, J. T.

AU - Harley, J. B.

AU - Bae, S. C.

AU - Vyse, T. J.

AU - Gilkeson, G. S.

AU - Gaffney, P. M.

AU - Moser, K. L.

AU - Putterman, C.

AU - Edberg, J. C.

AU - Brown, E. E.

AU - Ziegler, J.

AU - Langefeld, C. D.

AU - Zidovetzki, R.

AU - Jacob, C. O.

N1 - Funding Information: 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.

PY - 2009/7

Y1 - 2009/7

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AB - 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.

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

Abstract

Bibliographical note

Funding

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