title: Lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus.
abstract: BACKGROUND
  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 (GRS(s)).
  
  
  RESULTS
  Our results did not replicate those of the previous study at either the level of individual loci or the global level of GRS(s). GRS(s) 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.
  
  
  CONCLUSIONS
  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.
authors.forename: Elisa
authors.initials: E
authors.lastname: Alonso-Perez
authors.forename: Marian
authors.initials: M
authors.lastname: Suarez-Gestal
authors.forename: Manuel
authors.initials: M
authors.lastname: Calaza
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Blanco
authors.forename: Ana
authors.initials: A
authors.lastname: Suarez
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Santos
authors.forename: Chryssa
authors.initials: C
authors.lastname: Papasteriades
authors.forename: Patricia
authors.initials: P
authors.lastname: Carreira
authors.forename: Rudolf
authors.initials: R
authors.lastname: Pullmann
authors.forename: Josep
authors.initials: J
authors.lastname: Ordi-Ros
authors.forename: Maurizio
authors.initials: M
authors.lastname: Marchini
authors.forename: Fotini N
authors.initials: FN
authors.lastname: Skopouli
authors.forename: Marc
authors.initials: M
authors.lastname: Bijl
authors.forename: Nadia
authors.initials: N
authors.lastname: Barrizone
authors.forename: Gian Domenico
authors.initials: GD
authors.lastname: Sebastiani
authors.forename: Sergio
authors.initials: S
authors.lastname: Migliaresi
authors.forename: Torsten
authors.initials: T
authors.lastname: Witte
authors.forename: Bernard R
authors.initials: BR
authors.lastname: Lauwerys
authors.forename: Attila
authors.initials: A
authors.lastname: Kovacs
authors.forename: Sarka
authors.initials: S
authors.lastname: Ruzickova
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Gomez-Reino
authors.forename: Antonio
authors.initials: A
authors.lastname: Gonzalez
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D005060:Europe; D005260:Female; D005787:Gene Frequency; D040741:Genetic Load; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment / Q000379:methods* / Q000706:statistics & numerical data; D012307:Risk Factors; D012737:Sex Factors; D044465:White People / Q000235:genetics