Replication of recently identified systemic lupus erythematosus genetic associations: A case-control study

Marian Suarez-Gestal, Manuel Calaza, Emöke Endreffy, Rudolf Pullmann, Josep Ordi-Ros, Gian Domenico Sebastiani, Sarka Ruzickova, Maria Jose Santos, Chryssa Papasteriades, Maurizio Marchini, Fotini N. Skopouli, Ana Suarez, Francisco J. Blanco, Sandra D'Alfonso, Marc Bijl, Patricia Carreira, Torsten Witte, Sergio Migliaresi, Juan J. Gomez-Reino, Antonio GonzalezAttila Kovacs, Eva Balada, Ctibor Dostal, Filipe Vinagre, Iris Kappou-Rigatou, Raffaella Scorza, Maria Mavromati, Carmen Gutierrez, Ignacio Rego, Nadia Barizzone, Cees G. Kallenberg, Reinhold E. Schmidt

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Introduction: We aimed to replicate association of newly identified systemic lupus erythematosus (SLE) loci. Methods: We selected the most associated SNP in 10 SLE loci. These 10 SNPs were analysed in 1,579 patients with SLE and 1,726 controls of European origin by single-base extension. Comparison of allele frequencies between cases and controls was done with the Mantel-Haenszel approach to account for heterogeneity between sample collections. Results: A previously controversial association with a SNP in the TYK2 gene was replicated (odds ratio (OR) = 0.79, P = 2.5 × 10-5), as well as association with the X chromosome MECP2 gene (OR = 1.26, P = 0.00085 in women), which had only been reported in a single study, and association with four other loci, 1q25.1 (OR = 0.81, P = 0.0001), PXK (OR = 1.19, P = 0.0038), BANK1 (OR = 0.83, P = 0.006) and KIAA1542 (OR = 0.84, P = 0.001), which have been identified in a genome-wide association study, but not found in any other study. All these replications showed the same disease-associated allele as originally reported. No association was found with the LY9 SNP, which had been reported in a single study. Conclusions: Our results confirm nine SLE loci. For six of them, TYK2, MECP2, 1q25.1, PXK, BANK1 and KIAA1542, this replication is important. The other three loci, ITGAM, STAT4 and C8orf13-BLK, were already clearly confirmed. Our results also suggest that MECP2 association has no influence in the sex bias of SLE, contrary to what has been proposed. In addition, none of the other associations seems important in this respect.

Original languageEnglish
Article number69
JournalArthritis Research and Therapy
Volume11
Issue number3
DOIs
Publication statusPublished - May 14 2009

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Systemic Lupus Erythematosus
Case-Control Studies
Odds Ratio
Single Nucleotide Polymorphism
Sexism
X-Linked Genes
Genome-Wide Association Study
Gene Frequency
Alleles
Genes

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy
  • Medicine(all)

Cite this

Suarez-Gestal, M., Calaza, M., Endreffy, E., Pullmann, R., Ordi-Ros, J., Domenico Sebastiani, G., ... Schmidt, R. E. (2009). Replication of recently identified systemic lupus erythematosus genetic associations: A case-control study. Arthritis Research and Therapy, 11(3), [69]. https://doi.org/10.1186/ar2698

Replication of recently identified systemic lupus erythematosus genetic associations : A case-control study. / Suarez-Gestal, Marian; Calaza, Manuel; Endreffy, Emöke; Pullmann, Rudolf; Ordi-Ros, Josep; Domenico Sebastiani, Gian; Ruzickova, Sarka; Jose Santos, Maria; Papasteriades, Chryssa; Marchini, Maurizio; Skopouli, Fotini N.; Suarez, Ana; Blanco, Francisco J.; D'Alfonso, Sandra; Bijl, Marc; Carreira, Patricia; Witte, Torsten; Migliaresi, Sergio; Gomez-Reino, Juan J.; Gonzalez, Antonio; Kovacs, Attila; Balada, Eva; Dostal, Ctibor; Vinagre, Filipe; Kappou-Rigatou, Iris; Scorza, Raffaella; Mavromati, Maria; Gutierrez, Carmen; Rego, Ignacio; Barizzone, Nadia; Kallenberg, Cees G.; Schmidt, Reinhold E.

In: Arthritis Research and Therapy, Vol. 11, No. 3, 69, 14.05.2009.

Research output: Contribution to journalArticle

Suarez-Gestal, M, Calaza, M, Endreffy, E, Pullmann, R, Ordi-Ros, J, Domenico Sebastiani, G, Ruzickova, S, Jose Santos, M, Papasteriades, C, Marchini, M, Skopouli, FN, Suarez, A, Blanco, FJ, D'Alfonso, S, Bijl, M, Carreira, P, Witte, T, Migliaresi, S, Gomez-Reino, JJ, Gonzalez, A, Kovacs, A, Balada, E, Dostal, C, Vinagre, F, Kappou-Rigatou, I, Scorza, R, Mavromati, M, Gutierrez, C, Rego, I, Barizzone, N, Kallenberg, CG & Schmidt, RE 2009, 'Replication of recently identified systemic lupus erythematosus genetic associations: A case-control study', Arthritis Research and Therapy, vol. 11, no. 3, 69. https://doi.org/10.1186/ar2698
Suarez-Gestal, Marian ; Calaza, Manuel ; Endreffy, Emöke ; Pullmann, Rudolf ; Ordi-Ros, Josep ; Domenico Sebastiani, Gian ; Ruzickova, Sarka ; Jose Santos, Maria ; Papasteriades, Chryssa ; Marchini, Maurizio ; Skopouli, Fotini N. ; Suarez, Ana ; Blanco, Francisco J. ; D'Alfonso, Sandra ; Bijl, Marc ; Carreira, Patricia ; Witte, Torsten ; Migliaresi, Sergio ; Gomez-Reino, Juan J. ; Gonzalez, Antonio ; Kovacs, Attila ; Balada, Eva ; Dostal, Ctibor ; Vinagre, Filipe ; Kappou-Rigatou, Iris ; Scorza, Raffaella ; Mavromati, Maria ; Gutierrez, Carmen ; Rego, Ignacio ; Barizzone, Nadia ; Kallenberg, Cees G. ; Schmidt, Reinhold E. / Replication of recently identified systemic lupus erythematosus genetic associations : A case-control study. In: Arthritis Research and Therapy. 2009 ; Vol. 11, No. 3.
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abstract = "Introduction: We aimed to replicate association of newly identified systemic lupus erythematosus (SLE) loci. Methods: We selected the most associated SNP in 10 SLE loci. These 10 SNPs were analysed in 1,579 patients with SLE and 1,726 controls of European origin by single-base extension. Comparison of allele frequencies between cases and controls was done with the Mantel-Haenszel approach to account for heterogeneity between sample collections. Results: A previously controversial association with a SNP in the TYK2 gene was replicated (odds ratio (OR) = 0.79, P = 2.5 × 10-5), as well as association with the X chromosome MECP2 gene (OR = 1.26, P = 0.00085 in women), which had only been reported in a single study, and association with four other loci, 1q25.1 (OR = 0.81, P = 0.0001), PXK (OR = 1.19, P = 0.0038), BANK1 (OR = 0.83, P = 0.006) and KIAA1542 (OR = 0.84, P = 0.001), which have been identified in a genome-wide association study, but not found in any other study. All these replications showed the same disease-associated allele as originally reported. No association was found with the LY9 SNP, which had been reported in a single study. Conclusions: Our results confirm nine SLE loci. For six of them, TYK2, MECP2, 1q25.1, PXK, BANK1 and KIAA1542, this replication is important. The other three loci, ITGAM, STAT4 and C8orf13-BLK, were already clearly confirmed. Our results also suggest that MECP2 association has no influence in the sex bias of SLE, contrary to what has been proposed. In addition, none of the other associations seems important in this respect.",
author = "Marian Suarez-Gestal and Manuel Calaza and Em{\"o}ke Endreffy and Rudolf Pullmann and Josep Ordi-Ros and {Domenico Sebastiani}, Gian and Sarka Ruzickova and {Jose Santos}, Maria and Chryssa Papasteriades and Maurizio Marchini and Skopouli, {Fotini N.} and Ana Suarez and Blanco, {Francisco J.} and Sandra D'Alfonso and Marc Bijl and Patricia Carreira and Torsten Witte and Sergio Migliaresi and Gomez-Reino, {Juan J.} and Antonio Gonzalez and Attila Kovacs and Eva Balada and Ctibor Dostal and Filipe Vinagre and Iris Kappou-Rigatou and Raffaella Scorza and Maria Mavromati and Carmen Gutierrez and Ignacio Rego and Nadia Barizzone and Kallenberg, {Cees G.} and Schmidt, {Reinhold E.}",
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T1 - Replication of recently identified systemic lupus erythematosus genetic associations

T2 - A case-control study

AU - Suarez-Gestal, Marian

AU - Calaza, Manuel

AU - Endreffy, Emöke

AU - Pullmann, Rudolf

AU - Ordi-Ros, Josep

AU - Domenico Sebastiani, Gian

AU - Ruzickova, Sarka

AU - Jose Santos, Maria

AU - Papasteriades, Chryssa

AU - Marchini, Maurizio

AU - Skopouli, Fotini N.

AU - Suarez, Ana

AU - Blanco, Francisco J.

AU - D'Alfonso, Sandra

AU - Bijl, Marc

AU - Carreira, Patricia

AU - Witte, Torsten

AU - Migliaresi, Sergio

AU - Gomez-Reino, Juan J.

AU - Gonzalez, Antonio

AU - Kovacs, Attila

AU - Balada, Eva

AU - Dostal, Ctibor

AU - Vinagre, Filipe

AU - Kappou-Rigatou, Iris

AU - Scorza, Raffaella

AU - Mavromati, Maria

AU - Gutierrez, Carmen

AU - Rego, Ignacio

AU - Barizzone, Nadia

AU - Kallenberg, Cees G.

AU - Schmidt, Reinhold E.

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N2 - Introduction: We aimed to replicate association of newly identified systemic lupus erythematosus (SLE) loci. Methods: We selected the most associated SNP in 10 SLE loci. These 10 SNPs were analysed in 1,579 patients with SLE and 1,726 controls of European origin by single-base extension. Comparison of allele frequencies between cases and controls was done with the Mantel-Haenszel approach to account for heterogeneity between sample collections. Results: A previously controversial association with a SNP in the TYK2 gene was replicated (odds ratio (OR) = 0.79, P = 2.5 × 10-5), as well as association with the X chromosome MECP2 gene (OR = 1.26, P = 0.00085 in women), which had only been reported in a single study, and association with four other loci, 1q25.1 (OR = 0.81, P = 0.0001), PXK (OR = 1.19, P = 0.0038), BANK1 (OR = 0.83, P = 0.006) and KIAA1542 (OR = 0.84, P = 0.001), which have been identified in a genome-wide association study, but not found in any other study. All these replications showed the same disease-associated allele as originally reported. No association was found with the LY9 SNP, which had been reported in a single study. Conclusions: Our results confirm nine SLE loci. For six of them, TYK2, MECP2, 1q25.1, PXK, BANK1 and KIAA1542, this replication is important. The other three loci, ITGAM, STAT4 and C8orf13-BLK, were already clearly confirmed. Our results also suggest that MECP2 association has no influence in the sex bias of SLE, contrary to what has been proposed. In addition, none of the other associations seems important in this respect.

AB - Introduction: We aimed to replicate association of newly identified systemic lupus erythematosus (SLE) loci. Methods: We selected the most associated SNP in 10 SLE loci. These 10 SNPs were analysed in 1,579 patients with SLE and 1,726 controls of European origin by single-base extension. Comparison of allele frequencies between cases and controls was done with the Mantel-Haenszel approach to account for heterogeneity between sample collections. Results: A previously controversial association with a SNP in the TYK2 gene was replicated (odds ratio (OR) = 0.79, P = 2.5 × 10-5), as well as association with the X chromosome MECP2 gene (OR = 1.26, P = 0.00085 in women), which had only been reported in a single study, and association with four other loci, 1q25.1 (OR = 0.81, P = 0.0001), PXK (OR = 1.19, P = 0.0038), BANK1 (OR = 0.83, P = 0.006) and KIAA1542 (OR = 0.84, P = 0.001), which have been identified in a genome-wide association study, but not found in any other study. All these replications showed the same disease-associated allele as originally reported. No association was found with the LY9 SNP, which had been reported in a single study. Conclusions: Our results confirm nine SLE loci. For six of them, TYK2, MECP2, 1q25.1, PXK, BANK1 and KIAA1542, this replication is important. The other three loci, ITGAM, STAT4 and C8orf13-BLK, were already clearly confirmed. Our results also suggest that MECP2 association has no influence in the sex bias of SLE, contrary to what has been proposed. In addition, none of the other associations seems important in this respect.

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