TY - JOUR
T1 - Lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus
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, Emöke
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.
AB - 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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U2 - 10.1186/ar4585
DO - 10.1186/ar4585
M3 - Article
C2 - 24946689
AN - SCOPUS:84902740947
VL - 16
JO - Arthritis Research and Therapy
JF - Arthritis Research and Therapy
SN - 1478-6354
IS - 3
M1 - R128
ER -