Lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus

Elisa Alonso-Perez, Marian Suarez-Gestal, Manuel Calaza, Francisco J. Blanco, Ana Suarez, Maria J. Santos, Chryssa Papasteriades, Patricia Carreira, Rudolf Pullmann, Josep Ordi-Ros, Maurizio Marchini, Fotini N. Skopouli, Marc Bijl, Nadia Barrizone, Gian D. Sebastiani, Sergio Migliaresi, Torsten Witte, Bernard R. Lauwerys, Attila Kovacs, Sarka Ruzickova & 15 others Juan J. Gomez-Reino, Antonio Gonzalez, Myriam Liz, Iris Kappou-Rigatou, Lorenzo Beretta, Eva Balada, Cees G. Kallenberg, Filipe Vinagre, Maria Mavromati, Carmen Gutierrez, Ignacio Rego, Sandra D'Alfonso, Reinhold E. Schmidt, E. Endreffy, Ctibor Dostal

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Abstract

Introduction: We aimed to replicate a recent study which showed higher genetic risk load at 15 loci in men than in women with systemic lupus erythematosus (SLE). This difference was very significant, and it was interpreted as indicating that men require more genetic susceptibility than women to develop SLE.Methods: Nineteen SLE-associated loci (thirteen of which are shared with the previous study) were analyzed in 1,457 SLE patients and 1,728 healthy controls of European ancestry. Genetic risk load was calculated as sex-specific sum genetic risk scores (GRSs).Results: Our results did not replicate those of the previous study at either the level of individual loci or the global level of GRSs. GRSs were larger in women than in men (4.20 ± 1.07 in women vs. 3.27 ± 0.98 in men). This very significant difference (P <10-16) was more dependent on the six new loci not included in the previous study (59% of the difference) than on the thirteen loci that are shared (the remaining 41%). However, the 13 shared loci also showed a higher genetic risk load in women than in men in our study (P = 6.6 × 10-7), suggesting that heterogeneity of participants, in addition to different loci, contributed to the opposite results.Conclusion: Our results show the lack of a clear trend toward higher genetic risk in one of the sexes for the analyzed SLE loci. They also highlight several limitations of assessments of genetic risk load, including the possibility of ascertainment bias with loci discovered in studies that have included mainly women.

Original languageEnglish
Article numberR128
JournalArthritis Research and Therapy
Volume16
Issue number3
DOIs
Publication statusPublished - Jun 19 2014

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Genetic Load
Systemic Lupus Erythematosus
Genetic Predisposition to Disease

ASJC Scopus subject areas

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

Cite this

Alonso-Perez, E., Suarez-Gestal, M., Calaza, M., Blanco, F. J., Suarez, A., Santos, M. J., ... Dostal, C. (2014). Lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus. Arthritis Research and Therapy, 16(3), [R128]. https://doi.org/10.1186/ar4585

Lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus. / Alonso-Perez, Elisa; Suarez-Gestal, Marian; Calaza, Manuel; Blanco, Francisco J.; Suarez, Ana; Santos, Maria J.; Papasteriades, Chryssa; Carreira, Patricia; Pullmann, Rudolf; Ordi-Ros, Josep; Marchini, Maurizio; Skopouli, Fotini N.; Bijl, Marc; Barrizone, Nadia; Sebastiani, Gian D.; Migliaresi, Sergio; Witte, Torsten; Lauwerys, Bernard R.; Kovacs, Attila; Ruzickova, Sarka; Gomez-Reino, Juan J.; Gonzalez, Antonio; Liz, Myriam; Kappou-Rigatou, Iris; Beretta, Lorenzo; Balada, Eva; Kallenberg, Cees G.; Vinagre, Filipe; Mavromati, Maria; Gutierrez, Carmen; Rego, Ignacio; D'Alfonso, Sandra; Schmidt, Reinhold E.; Endreffy, E.; Dostal, Ctibor.

In: Arthritis Research and Therapy, Vol. 16, No. 3, R128, 19.06.2014.

Research output: Contribution to journalArticle

Alonso-Perez, E, Suarez-Gestal, M, Calaza, M, Blanco, FJ, Suarez, A, Santos, MJ, Papasteriades, C, Carreira, P, Pullmann, R, Ordi-Ros, J, Marchini, M, Skopouli, FN, Bijl, M, Barrizone, N, Sebastiani, GD, Migliaresi, S, Witte, T, Lauwerys, BR, Kovacs, A, Ruzickova, S, Gomez-Reino, JJ, Gonzalez, A, Liz, M, Kappou-Rigatou, I, Beretta, L, Balada, E, Kallenberg, CG, Vinagre, F, Mavromati, M, Gutierrez, C, Rego, I, D'Alfonso, S, Schmidt, RE, Endreffy, E & Dostal, C 2014, 'Lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus', Arthritis Research and Therapy, vol. 16, no. 3, R128. https://doi.org/10.1186/ar4585
Alonso-Perez E, Suarez-Gestal M, Calaza M, Blanco FJ, Suarez A, Santos MJ et al. Lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus. Arthritis Research and Therapy. 2014 Jun 19;16(3). R128. https://doi.org/10.1186/ar4585
Alonso-Perez, Elisa ; Suarez-Gestal, Marian ; Calaza, Manuel ; Blanco, Francisco J. ; Suarez, Ana ; Santos, Maria J. ; Papasteriades, Chryssa ; Carreira, Patricia ; Pullmann, Rudolf ; Ordi-Ros, Josep ; Marchini, Maurizio ; Skopouli, Fotini N. ; Bijl, Marc ; Barrizone, Nadia ; Sebastiani, Gian D. ; Migliaresi, Sergio ; Witte, Torsten ; Lauwerys, Bernard R. ; Kovacs, Attila ; Ruzickova, Sarka ; Gomez-Reino, Juan J. ; Gonzalez, Antonio ; Liz, Myriam ; Kappou-Rigatou, Iris ; Beretta, Lorenzo ; Balada, Eva ; Kallenberg, Cees G. ; Vinagre, Filipe ; Mavromati, Maria ; Gutierrez, Carmen ; Rego, Ignacio ; D'Alfonso, Sandra ; Schmidt, Reinhold E. ; Endreffy, E. ; Dostal, Ctibor. / Lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus. In: Arthritis Research and Therapy. 2014 ; Vol. 16, No. 3.
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abstract = "Introduction: We aimed to replicate a recent study which showed higher genetic risk load at 15 loci in men than in women with systemic lupus erythematosus (SLE). This difference was very significant, and it was interpreted as indicating that men require more genetic susceptibility than women to develop SLE.Methods: Nineteen SLE-associated loci (thirteen of which are shared with the previous study) were analyzed in 1,457 SLE patients and 1,728 healthy controls of European ancestry. Genetic risk load was calculated as sex-specific sum genetic risk scores (GRSs).Results: Our results did not replicate those of the previous study at either the level of individual loci or the global level of GRSs. GRSs were larger in women than in men (4.20 ± 1.07 in women vs. 3.27 ± 0.98 in men). This very significant difference (P <10-16) was more dependent on the six new loci not included in the previous study (59{\%} of the difference) than on the thirteen loci that are shared (the remaining 41{\%}). However, the 13 shared loci also showed a higher genetic risk load in women than in men in our study (P = 6.6 × 10-7), suggesting that heterogeneity of participants, in addition to different loci, contributed to the opposite results.Conclusion: Our results show the lack of a clear trend toward higher genetic risk in one of the sexes for the analyzed SLE loci. They also highlight several limitations of assessments of genetic risk load, including the possibility of ascertainment bias with loci discovered in studies that have included mainly women.",
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AU - Alonso-Perez, Elisa

AU - Suarez-Gestal, Marian

AU - Calaza, Manuel

AU - Blanco, Francisco J.

AU - Suarez, Ana

AU - Santos, Maria J.

AU - Papasteriades, Chryssa

AU - Carreira, Patricia

AU - Pullmann, Rudolf

AU - Ordi-Ros, Josep

AU - Marchini, Maurizio

AU - Skopouli, Fotini N.

AU - Bijl, Marc

AU - Barrizone, Nadia

AU - Sebastiani, Gian D.

AU - Migliaresi, Sergio

AU - Witte, Torsten

AU - Lauwerys, Bernard R.

AU - Kovacs, Attila

AU - Ruzickova, Sarka

AU - Gomez-Reino, Juan J.

AU - Gonzalez, Antonio

AU - Liz, Myriam

AU - Kappou-Rigatou, Iris

AU - Beretta, Lorenzo

AU - Balada, Eva

AU - Kallenberg, Cees G.

AU - Vinagre, Filipe

AU - Mavromati, Maria

AU - Gutierrez, Carmen

AU - Rego, Ignacio

AU - D'Alfonso, Sandra

AU - Schmidt, Reinhold E.

AU - Endreffy, E.

AU - Dostal, Ctibor

PY - 2014/6/19

Y1 - 2014/6/19

N2 - Introduction: We aimed to replicate a recent study which showed higher genetic risk load at 15 loci in men than in women with systemic lupus erythematosus (SLE). This difference was very significant, and it was interpreted as indicating that men require more genetic susceptibility than women to develop SLE.Methods: Nineteen SLE-associated loci (thirteen of which are shared with the previous study) were analyzed in 1,457 SLE patients and 1,728 healthy controls of European ancestry. Genetic risk load was calculated as sex-specific sum genetic risk scores (GRSs).Results: Our results did not replicate those of the previous study at either the level of individual loci or the global level of GRSs. GRSs were larger in women than in men (4.20 ± 1.07 in women vs. 3.27 ± 0.98 in men). This very significant difference (P <10-16) was more dependent on the six new loci not included in the previous study (59% of the difference) than on the thirteen loci that are shared (the remaining 41%). However, the 13 shared loci also showed a higher genetic risk load in women than in men in our study (P = 6.6 × 10-7), suggesting that heterogeneity of participants, in addition to different loci, contributed to the opposite results.Conclusion: Our results show the lack of a clear trend toward higher genetic risk in one of the sexes for the analyzed SLE loci. They also highlight several limitations of assessments of genetic risk load, including the possibility of ascertainment bias with loci discovered in studies that have included mainly women.

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