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

Marian Suarez-Gestal; Manuel Calaza; Emoeke 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 Gonzalez; European Consortium SLE DNA

doi:10.1186/ar2698

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

Marian Suarez-Gestal, Manuel Calaza, Emoeke 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 Gonzalez^*European Consortium SLE DNA

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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 x 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 language	English
Article number	69
Number of pages	9
Journal	Arthritis Research and Therapy
Volume	11
Issue number	3
DOIs	https://doi.org/10.1186/ar2698
Publication status	Published - 14-May-2009

Keywords

GENOME-WIDE ASSOCIATION
RHEUMATOID-ARTHRITIS
VARIANTS
RISK
STAT4
SUSCEPTIBILITY
POLYMORPHISMS
ITGAM
MECP2
SLE

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Suarez-Gestal, M., Calaza, M., Endreffy, E., Pullmann, R., Ordi-Ros, J., Sebastiani, G. D., Ruzickova, S., Santos, M. J., Papasteriades, C., Marchini, M., Skopouli, F. N., Suarez, A., Blanco, F. J., D'Alfonso, S., Bijl, M., Carreira, P., Witte, T., Migliaresi, S., Gomez-Reino, J. J., ... European Consortium SLE DNA (2009). Replication of recently identified systemic lupus erythematosus genetic associations: a case-control study. Arthritis Research and Therapy, 11(3), Article 69. https://doi.org/10.1186/ar2698

@article{a92a00588d3247b6aa401a809ce9cc61,

title = "Replication of recently identified systemic lupus erythematosus genetic associations: a case-control study",

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 x 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.",

keywords = "GENOME-WIDE ASSOCIATION, RHEUMATOID-ARTHRITIS, VARIANTS, RISK, STAT4, SUSCEPTIBILITY, POLYMORPHISMS, ITGAM, MECP2, SLE",

author = "Marian Suarez-Gestal and Manuel Calaza and Emoeke Endreffy and Rudolf Pullmann and Josep Ordi-Ros and Sebastiani, {Gian Domenico} and Sarka Ruzickova and Santos, {Maria Jose} 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 {European Consortium SLE DNA}",

year = "2009",

month = may,

day = "14",

doi = "10.1186/ar2698",

language = "English",

volume = "11",

journal = "Arthritis Research and Therapy",

issn = "1478-6354",

publisher = "BioMed Central Ltd.",

number = "3",

}

Suarez-Gestal, M, Calaza, M, Endreffy, E, Pullmann, R, Ordi-Ros, J, Sebastiani, GD, Ruzickova, S, Santos, MJ, 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 & European Consortium SLE DNA 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

TY - JOUR

T1 - Replication of recently identified systemic lupus erythematosus genetic associations

T2 - a case-control study

AU - Suarez-Gestal, Marian

AU - Calaza, Manuel

AU - Endreffy, Emoeke

AU - Pullmann, Rudolf

AU - Ordi-Ros, Josep

AU - Sebastiani, Gian Domenico

AU - Ruzickova, Sarka

AU - Santos, Maria Jose

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 - European Consortium SLE DNA

PY - 2009/5/14

Y1 - 2009/5/14

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 x 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 x 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.

KW - GENOME-WIDE ASSOCIATION

KW - RHEUMATOID-ARTHRITIS

KW - VARIANTS

KW - RISK

KW - STAT4

KW - SUSCEPTIBILITY

KW - POLYMORPHISMS

KW - ITGAM

KW - MECP2

KW - SLE

U2 - 10.1186/ar2698

DO - 10.1186/ar2698

M3 - Article

C2 - 19442287

SN - 1478-6354

VL - 11

JO - Arthritis Research and Therapy

JF - Arthritis Research and Therapy

IS - 3

M1 - 69

ER -

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

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Keywords

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