Replication of the BANK1 genetic association with systemic lupus erythematosus in a European-derived population

L. Guo, H. Deshmukh, R. Lu, G. S. Vidal, J. A. Kelly, K. M. Kaufman, N. Dominguez, W. Klein, X. Kim-Howard, G. R. Bruner, R. H. Scofield, K. L. Moser, P. M. Gaffney, I. M. Dozmorov, G. S. Gilkeson, E. K. Wakeland, Q. Z. Li, C. D. Langefeld, M. C. Marion, A. H. Williams & 16 others J. Divers, G. S. Alarcón, E. E. Brown, R. P. Kimberly, J. C. Edberg, R. Ramsey-Goldman, J. D. Reveille, G. McGwin, L. M. Vilá, M. A. Petri, T. J. Vyse, J. T. Merrill, J. A. James, S. K. Nath, J. B. Harley, J. M. Guthridge

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease with highly variable clinical presentation. Patients suffer from immunological abnormalities that target T-cell, B-cell and accessory cell functions. B cells are hyperactive in SLE patients. An adapter protein expressed in B cells called BANK1 (B-cell scaffold protein with ankyrin repeats) was reported in a previous study to be associated with SLE in a European population. The objective of this study was to assess the BANK1 genotype-phenotype association in an independent replication sample. We genotyped 38 single nucleotide polymorphisms (SNPs) in BANK1 on 1892 European-derived SLE patients and 2652 European-derived controls. The strongest associations with SLE and BANK1 were at rs17266594 (corrected P-value = 1.97 × 10-5, odds ratio (OR) = 1.22, 95% CI 1.12-1.34) and rs10516487 (corrected P-value = 2.59 × 10-5, OR = 1.22, 95% CI 1.11-1.34). Our findings suggest that the association is explained by these two SNPs, confirming previous reports that these polymorphisms contribute to the risk of developing lupus. Analysis of patient subsets enriched for hematological, immunological and renal ACR criteria or the levels of autoantibodies, such as anti-RNP A and anti-SmRNP, uncovers additional BANK1 associations. Our results suggest that BANK1 polymorphisms alter immune system development and function to increase the risk for developing lupus.

Original languageEnglish (US)
Pages (from-to)531-538
Number of pages8
JournalGenes and Immunity
Volume10
Issue number5
DOIs
StatePublished - 2009

Fingerprint

Systemic Lupus Erythematosus
B-Lymphocytes
Population
Single Nucleotide Polymorphism
Odds Ratio
Ankyrin Repeat
Genetic Association Studies
Autoantibodies
Autoimmune Diseases
Immune System
Proteins
T-Lymphocytes
Kidney

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Cite this

Guo, L., Deshmukh, H., Lu, R., Vidal, G. S., Kelly, J. A., Kaufman, K. M., ... Guthridge, J. M. (2009). Replication of the BANK1 genetic association with systemic lupus erythematosus in a European-derived population. Genes and Immunity, 10(5), 531-538. https://doi.org/10.1038/gene.2009.18

Replication of the BANK1 genetic association with systemic lupus erythematosus in a European-derived population. / Guo, L.; Deshmukh, H.; Lu, R.; Vidal, G. S.; Kelly, J. A.; Kaufman, K. M.; Dominguez, N.; Klein, W.; Kim-Howard, X.; Bruner, G. R.; Scofield, R. H.; Moser, K. L.; Gaffney, P. M.; Dozmorov, I. M.; Gilkeson, G. S.; Wakeland, E. K.; Li, Q. Z.; Langefeld, C. D.; Marion, M. C.; Williams, A. H.; Divers, J.; Alarcón, G. S.; Brown, E. E.; Kimberly, R. P.; Edberg, J. C.; Ramsey-Goldman, R.; Reveille, J. D.; McGwin, G.; Vilá, L. M.; Petri, M. A.; Vyse, T. J.; Merrill, J. T.; James, J. A.; Nath, S. K.; Harley, J. B.; Guthridge, J. M.

In: Genes and Immunity, Vol. 10, No. 5, 2009, p. 531-538.

Research output: Contribution to journalArticle

Guo, L, Deshmukh, H, Lu, R, Vidal, GS, Kelly, JA, Kaufman, KM, Dominguez, N, Klein, W, Kim-Howard, X, Bruner, GR, Scofield, RH, Moser, KL, Gaffney, PM, Dozmorov, IM, Gilkeson, GS, Wakeland, EK, Li, QZ, Langefeld, CD, Marion, MC, Williams, AH, Divers, J, Alarcón, GS, Brown, EE, Kimberly, RP, Edberg, JC, Ramsey-Goldman, R, Reveille, JD, McGwin, G, Vilá, LM, Petri, MA, Vyse, TJ, Merrill, JT, James, JA, Nath, SK, Harley, JB & Guthridge, JM 2009, 'Replication of the BANK1 genetic association with systemic lupus erythematosus in a European-derived population', Genes and Immunity, vol. 10, no. 5, pp. 531-538. https://doi.org/10.1038/gene.2009.18
Guo, L. ; Deshmukh, H. ; Lu, R. ; Vidal, G. S. ; Kelly, J. A. ; Kaufman, K. M. ; Dominguez, N. ; Klein, W. ; Kim-Howard, X. ; Bruner, G. R. ; Scofield, R. H. ; Moser, K. L. ; Gaffney, P. M. ; Dozmorov, I. M. ; Gilkeson, G. S. ; Wakeland, E. K. ; Li, Q. Z. ; Langefeld, C. D. ; Marion, M. C. ; Williams, A. H. ; Divers, J. ; Alarcón, G. S. ; Brown, E. E. ; Kimberly, R. P. ; Edberg, J. C. ; Ramsey-Goldman, R. ; Reveille, J. D. ; McGwin, G. ; Vilá, L. M. ; Petri, M. A. ; Vyse, T. J. ; Merrill, J. T. ; James, J. A. ; Nath, S. K. ; Harley, J. B. ; Guthridge, J. M. / Replication of the BANK1 genetic association with systemic lupus erythematosus in a European-derived population. In: Genes and Immunity. 2009 ; Vol. 10, No. 5. pp. 531-538.
@article{ee0792abb0f042c4bc98606f001b9cb1,
title = "Replication of the BANK1 genetic association with systemic lupus erythematosus in a European-derived population",
abstract = "Systemic lupus erythematosus (SLE) is an autoimmune disease with highly variable clinical presentation. Patients suffer from immunological abnormalities that target T-cell, B-cell and accessory cell functions. B cells are hyperactive in SLE patients. An adapter protein expressed in B cells called BANK1 (B-cell scaffold protein with ankyrin repeats) was reported in a previous study to be associated with SLE in a European population. The objective of this study was to assess the BANK1 genotype-phenotype association in an independent replication sample. We genotyped 38 single nucleotide polymorphisms (SNPs) in BANK1 on 1892 European-derived SLE patients and 2652 European-derived controls. The strongest associations with SLE and BANK1 were at rs17266594 (corrected P-value = 1.97 × 10-5, odds ratio (OR) = 1.22, 95{\%} CI 1.12-1.34) and rs10516487 (corrected P-value = 2.59 × 10-5, OR = 1.22, 95{\%} CI 1.11-1.34). Our findings suggest that the association is explained by these two SNPs, confirming previous reports that these polymorphisms contribute to the risk of developing lupus. Analysis of patient subsets enriched for hematological, immunological and renal ACR criteria or the levels of autoantibodies, such as anti-RNP A and anti-SmRNP, uncovers additional BANK1 associations. Our results suggest that BANK1 polymorphisms alter immune system development and function to increase the risk for developing lupus.",
author = "L. Guo and H. Deshmukh and R. Lu and Vidal, {G. S.} and Kelly, {J. A.} and Kaufman, {K. M.} and N. Dominguez and W. Klein and X. Kim-Howard and Bruner, {G. R.} and Scofield, {R. H.} and Moser, {K. L.} and Gaffney, {P. M.} and Dozmorov, {I. M.} and Gilkeson, {G. S.} and Wakeland, {E. K.} and Li, {Q. Z.} and Langefeld, {C. D.} and Marion, {M. C.} and Williams, {A. H.} and J. Divers and Alarc{\'o}n, {G. S.} and Brown, {E. E.} and Kimberly, {R. P.} and Edberg, {J. C.} and R. Ramsey-Goldman and Reveille, {J. D.} and G. McGwin and Vil{\'a}, {L. M.} and Petri, {M. A.} and Vyse, {T. J.} and Merrill, {J. T.} and James, {J. A.} and Nath, {S. K.} and Harley, {J. B.} and Guthridge, {J. M.}",
year = "2009",
doi = "10.1038/gene.2009.18",
language = "English (US)",
volume = "10",
pages = "531--538",
journal = "Genes and Immunity",
issn = "1466-4879",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Replication of the BANK1 genetic association with systemic lupus erythematosus in a European-derived population

AU - Guo, L.

AU - Deshmukh, H.

AU - Lu, R.

AU - Vidal, G. S.

AU - Kelly, J. A.

AU - Kaufman, K. M.

AU - Dominguez, N.

AU - Klein, W.

AU - Kim-Howard, X.

AU - Bruner, G. R.

AU - Scofield, R. H.

AU - Moser, K. L.

AU - Gaffney, P. M.

AU - Dozmorov, I. M.

AU - Gilkeson, G. S.

AU - Wakeland, E. K.

AU - Li, Q. Z.

AU - Langefeld, C. D.

AU - Marion, M. C.

AU - Williams, A. H.

AU - Divers, J.

AU - Alarcón, G. S.

AU - Brown, E. E.

AU - Kimberly, R. P.

AU - Edberg, J. C.

AU - Ramsey-Goldman, R.

AU - Reveille, J. D.

AU - McGwin, G.

AU - Vilá, L. M.

AU - Petri, M. A.

AU - Vyse, T. J.

AU - Merrill, J. T.

AU - James, J. A.

AU - Nath, S. K.

AU - Harley, J. B.

AU - Guthridge, J. M.

PY - 2009

Y1 - 2009

N2 - Systemic lupus erythematosus (SLE) is an autoimmune disease with highly variable clinical presentation. Patients suffer from immunological abnormalities that target T-cell, B-cell and accessory cell functions. B cells are hyperactive in SLE patients. An adapter protein expressed in B cells called BANK1 (B-cell scaffold protein with ankyrin repeats) was reported in a previous study to be associated with SLE in a European population. The objective of this study was to assess the BANK1 genotype-phenotype association in an independent replication sample. We genotyped 38 single nucleotide polymorphisms (SNPs) in BANK1 on 1892 European-derived SLE patients and 2652 European-derived controls. The strongest associations with SLE and BANK1 were at rs17266594 (corrected P-value = 1.97 × 10-5, odds ratio (OR) = 1.22, 95% CI 1.12-1.34) and rs10516487 (corrected P-value = 2.59 × 10-5, OR = 1.22, 95% CI 1.11-1.34). Our findings suggest that the association is explained by these two SNPs, confirming previous reports that these polymorphisms contribute to the risk of developing lupus. Analysis of patient subsets enriched for hematological, immunological and renal ACR criteria or the levels of autoantibodies, such as anti-RNP A and anti-SmRNP, uncovers additional BANK1 associations. Our results suggest that BANK1 polymorphisms alter immune system development and function to increase the risk for developing lupus.

AB - Systemic lupus erythematosus (SLE) is an autoimmune disease with highly variable clinical presentation. Patients suffer from immunological abnormalities that target T-cell, B-cell and accessory cell functions. B cells are hyperactive in SLE patients. An adapter protein expressed in B cells called BANK1 (B-cell scaffold protein with ankyrin repeats) was reported in a previous study to be associated with SLE in a European population. The objective of this study was to assess the BANK1 genotype-phenotype association in an independent replication sample. We genotyped 38 single nucleotide polymorphisms (SNPs) in BANK1 on 1892 European-derived SLE patients and 2652 European-derived controls. The strongest associations with SLE and BANK1 were at rs17266594 (corrected P-value = 1.97 × 10-5, odds ratio (OR) = 1.22, 95% CI 1.12-1.34) and rs10516487 (corrected P-value = 2.59 × 10-5, OR = 1.22, 95% CI 1.11-1.34). Our findings suggest that the association is explained by these two SNPs, confirming previous reports that these polymorphisms contribute to the risk of developing lupus. Analysis of patient subsets enriched for hematological, immunological and renal ACR criteria or the levels of autoantibodies, such as anti-RNP A and anti-SmRNP, uncovers additional BANK1 associations. Our results suggest that BANK1 polymorphisms alter immune system development and function to increase the risk for developing lupus.

UR - http://www.scopus.com/inward/record.url?scp=67849097327&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67849097327&partnerID=8YFLogxK

U2 - 10.1038/gene.2009.18

DO - 10.1038/gene.2009.18

M3 - Article

VL - 10

SP - 531

EP - 538

JO - Genes and Immunity

JF - Genes and Immunity

SN - 1466-4879

IS - 5

ER -